872 hot topic(s) found with the query "Genetic testing"
Global health for rare diseases through primary care
(Posted: Jun 21, 2024 8AM)
From the article: " Genetic testing shows promise in diagnosing people with rare diseases, as over 72% of rare diseases have a genetic basis. Next-generation sequencing and other technologies have facilitated the time-effective and cost-effective diagnosis of most genetic diseases, but substantial challenges hinder widespread adoption. The lack of genetic workforce capacity is a global concern, even in high-income countries, with many regions and countries lacking sufficient genetic expertise. The low reimbursement by governments and private insurers for genetic services also poses an additional barrier. The combination of these factors prevent primary care providers from referring people with suspected rare disease to specialists, which delays diagnosis and treatment. "
Implications of Provider Specialty, Test Type, and Demographic Factors on Genetic Testing Outcomes for Patients with Autism Spectrum Disorder
(Posted: Jun 18, 2024 4PM)
From the abstract: "A minority of patients with autism spectrum disorder (ASD) are offered genetic testing by their providers or referred for genetics evaluation despite published guidelines and consensus statements supporting genetics-informed care for this population. This study aimed to investigate the ordering habits of providers of different specialties and to additionally assess the diagnostic utility of genetic testing by test type, patient sex, and race and ethnicity. "
Family communication of cancer genetic test results in an ethnically diverse population: a qualitative exploration of more than 200 patients
(Posted: Jun 06, 2024 2PM)
From the abstract: " Previous research on family communication of cancer genetic test results has primarily focused on non-Hispanic White patients with high-risk pathogenic variants (PV). There are limited data on patient communication of moderate-risk PVs, variants of uncertain significance (VUS), and negative results. This qualitative study examined communication of positive, negative, and VUS hereditary cancer multi-gene panel (MGP) results in an ethnically and socioeconomically diverse population. "
Genetic Testing for Global Developmental Delay in Early Childhood
(Posted: Jun 06, 2024 2PM)
From the article: "What are the implications of genetic testing for global developmental delay (GDD) in early childhood? Findings: In this cohort study of 434 children with GDD, a diagnostic positivity rate of 61% was identified when using trio whole exome sequencing combined with copy number variation sequencing. A thorough analysis expanded the scope of indications for genetic testing, and the pathogenesis of GDD was further elucidated using a bioinformatics approach. Meaning: These findings suggest that early use of combined genetic testing for GDD may diminish the misdiagnosis rate, elucidate the etiologic diagnosis, and lay the groundwork for identifying novel early diagnostic biomarkers and intervention targets. "
Healthcare utilization and behavior changes following workplace genetic testing at a large U.S. healthcare system
(Posted: May 08, 2024 11AM)
From the abstract: " This study explored employee health behavior changes and healthcare utilization following workplace genetic testing (wGT). Wellness program-associated wGT seeks to improve employee health, but related health implications are unknown. Methods: Employees of a large U.S. healthcare system offering wGT (cancer, heart disease, and pharmacogenomics - PGx) were sent electronic surveys. Self-reported data from those who received test results were analyzed. Descriptive statistics characterized responses, while logistic regression analyses explored correlates of responses to wGT."
Expanding Applications of Clinical Genetic Testing - Ethical Challenges.
(Posted: Apr 18, 2024 8AM)
From the article: "Thanks to advances in human genomics, both technological and discovery-based, genetic and genomic testing (which we will refer to collectively as “genetic testing”) are playing an increasingly important role in clinical care. Although genetic testing has long been recognized as raising thorny ethical dilemmas, the widening scope and scale of genetic tests are reshaping old concerns and posing new challenges. Moreover, the need to address these ethical challenges is no longer restricted to clinicians in particular niches, instead becoming immediately relevant for all clinicians. "
Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.
Gabrielle Lemire et al. Am J Hum Genet 2024 4
(Posted: Apr 09, 2024 8AM)
From the abstract: "Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). "
Future implications of polygenic risk scores for life insurance underwriting.
Tatiane Yanes et al. NPJ Genom Med 2024 3 (1) 25
(Posted: Apr 01, 2024 9AM)
From the abstract: "As PGS is increasingly utilized in research and clinical practice, it is pivotal that careful consideration is given to the potential insurance implications of PGS to ensure consumer protection against GD. For the full potential benefits of PGS to be realized, and its clinical utility determined across various use cases, individuals will need to be confident that they can participate in research studies and access clinical genetic testing without fear of insurance discrimination. Clarification is needed regarding the extent to which existing protections and legislation relating to monogenic testing may also extend to PGS test results. "
What to Know About Lynch Syndrome
ThedaCare Genetic Counseling, March 2024
(Posted: Apr 01, 2024 9AM)
From the article: " While it is impossible to change our genes, with knowledge comes power. In the case of Lynch syndrome, a genetic condition that can increase a person’s risk for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening, as well as genetic testing, when recommended."
Applications of genome sequencing as a single platform for clinical constitutional genetic testing
Y Yang et al, GIM Open, March 20, 2024
(Posted: Mar 27, 2024 1PM)
From the abstract: "The number of human disease genes has dramatically increased over the past decade, largely fueled by ongoing advances in sequencing technologies. In parallel, the number of available clinical genetic tests has also increased, including exome sequencing for undiagnosed diseases. Although most clinical sequencing tests have been centered on enrichment-based multigene panels and exome sequencing, the continued improvements in performance and throughput of genome sequencing suggest that this technology is emerging as a potential platform for routine clinical genetic testing. "
Lynch Syndrome Ups Risk for Colorectal, Other Cancers
E Herlache, Cancer Care, March 2024
(Posted: Mar 23, 2024 6AM)
From the article: "It’s impossible to change our genes, but with knowledge comes power. In the case of Lynch syndrome, a genetic condition that ups people’s risks for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening as well as genetic testing, when warranted. Lynch syndrome puts a person at a higher risk of developing colorectal, uterine, and ovarian cancer. It’s also associated with other cancers, including kidney, stomach, bladder, brain, prostate, and pancreatic cancer. "
Systematic reanalysis of genomic data by diagnostic laboratories: a scoping review of ethical, economic, legal and (psycho)social implications.
Marije A van der Geest et al. Eur J Hum Genet 2024 3
(Posted: Mar 18, 2024 9AM)
From the abstract: "In total, we identified nine ELSI aspects, such as (perceived) professional responsibilities, implications for consent and cost-effectiveness. The identified ELSI aspects brought forward necessary trade-offs for GHPs to consciously take into account when considering responsible implementation of systematic reanalysis of NGS data in routine diagnostics, balancing the various strains on their laboratories and personnel while creating optimal results for new and former patients. "
Researchers optimize genetic tests for diverse populations to tackle health disparities
NIH, February 2024
(Posted: Mar 01, 2024 0PM)
From the website: " To prevent an emerging genomic technology from contributing to health disparities, a scientific team funded by the National Institutes of Health has devised new ways to improve a genetic testing method called a polygenic risk score. Since polygenic risk scores have not been effective for all populations, the researchers recalibrated these genetic tests using ancestrally diverse genomic data. As reported in Nature Medicine, the optimized tests provide a more accurate assessment of disease risk across diverse populations."
Evidence review and considerations for use of first line genome sequencing to diagnose rare genetic disorders.
Kristen M Wigby et al. NPJ Genom Med 2024 2 (1) 15
(Posted: Feb 29, 2024 8AM)
From the abstract: "Seventy-one studies met inclusion criteria, comprising over 13,000 patients who received GS in one of the following settings: hospitalized pediatric patients, pediatric outpatients, adult outpatients, or mixed. GS was the first-line test in 38% (27/71). The unweighted mean DY of first-line GS was 45% (12–73%), 33% (6–86%) in cohorts with prior genetic testing, and 33% (9–60%) in exome-negative cohorts. Clinical utility was reported in 81% of first-line GS studies in hospitalized pediatric patients. "
Genetic Testing: The Good, the Bad, and the Costly
R Ronanki, Forbes, February 2024
(Posted: Feb 16, 2024 4PM)
From the article: " Genetic testing pathways are rife with uncertainties. Predictive tests often yield probabilistic results, not definitive answers, leaving patients uncertain, especially when no effective treatments or therapies exist for their conditions. Despite the many scientific advances in genetics, researchers have only identified a small fraction of the genetic component of most diseases. Therefore, genetic tests for many diseases are developed on the basis of limited scientific information and may not yet provide valid or useful results to individuals who are tested.”
Understanding perceptions of tumor genomic profile testing in Black/African American cancer patients in a qualitative study: the role of medical mistrust, provider communication, and family support
CC Luck et al, J Comm Genetics, Feb 16, 2024
(Posted: Feb 16, 2024 4PM)
From the abstract: "Tumor genomic profiling (TGP) examines genes and somatic mutations specific to a patient’s tumor to identify targets for cancer treatments but can also uncover secondary hereditary (germline) mutations. Most patients are unprepared to make complex decisions related to this information. Black/African American (AA) cancer patients are especially at risk because of lower health literacy, higher levels of medical mistrust, and lower awareness and knowledge of genetic testing. But little is known about their TGP attitudes or preferences. "
Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.
Fangjian Guo et al. JAMA Netw Open 2024 2 (2) e2356078
(Posted: Feb 15, 2024 9AM)
From the abstract: "Is a population-wide genetic testing strategy more cost-effective than the current family history–based testing strategy for breast and ovarian cancer prevention? This economic evaluation found that population-based BRCA1, BRCA2, and PALB2 testing among unselected women was cost-effective for the prevention of breast and ovarian cancer and remained cost-effective in extensive 1-way sensitivity analyses. Population-wide genetic testing was 100% cost-effective for all the simulations in probabilistic sensitivity analyses; it became cost-inefficient only when the cost of the test exceeded a certain threshold ($825). The findings support the need for a shift toward more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management. "
Overcoming barriers to equitable genomic healthcare
KM Girisha, EJHG, February 13, 2024
(Posted: Feb 13, 2024 9AM)
From the article: "We all recognize the pivotal role of next-generation sequencing in the diagnosis and discovery of rare diseases that are majorly genetic in origin. While limited access might be the result of economic constraints in the three-fourths of the global population, it might also be due to infrastructure (genetic testing laboratories) or trained manpower (genome analysts) in other situations. "
Heart Disease Risk Higher with Genetic Variant Plus Even Slightly Elevated Cholesterol
Inside Precision Medicine, February 2, 2023
(Posted: Feb 03, 2024 8AM)
From the article: " Even people with moderately elevated low-density lipoprotein cholesterol (LDL-C) have higher risk of heart disease if they also had a variant for familial hypercholesterolemia (FH), according to new research. The long-term study included over 20,000 patients and reinforces the value of genetic testing for this condition."
Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol
Y Zhang et al, JAMA Cardio, January 31, 2023
(Posted: Feb 01, 2024 9AM)
From the abstract: "How do familial hypercholesterolemia (FH) genetic variants modify coronary heart disease (CHD) risk among adults with moderate (LDL-C 130-189 mg/dL) and severe (LDL-C=190 mg/dL) hypercholesterolemia? In this pooled cohort study of 21?426 participants followed up with for a median of 18 years, FH variants were associated with a 2-fold higher CHD risk, even among individuals with moderately elevated LDL-C. The increased CHD risk appeared to be largely explained by the substantially higher lifetime cumulative LDL-C exposure in those with an FH variant vs those without. The findings suggest that genetic testing for FH may help refine risk stratification beyond LDL-C alone; clinical research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening. "
Prenatal Genetic Testing Is Rapidly Evolving. Here’s Why That Matters.
M Holmes, Huffington Post, January 12, 2024
(Posted: Jan 14, 2024 10AM)
From the article: " In the context of pregnancy, the role of DNA testing is to uncover genetic disease in a fetus. (An additional bonus for parents is learning the baby’s sex, which many are eager to know.) Unfortunately, genetic testing in pregnancy often isn’t as conclusive or uncomplicated as the DNA testing police use to determine whether someone was at the scene of a crime."
Managing genetic information sharing at family and population level
A McNeill, EJHG, January 4, 2023
(Posted: Jan 05, 2024 8AM)
From the article: "The process by which the “at risk” relatives of a person with a genetic condition should be notified of the possible need for them to have genetic testing has long been controversial. At present, it is common practice to request the proband to inform relatives of the genetic condition, treatment and testing options. Uptake of cascade testing is generally low, and dissemination of the genetic information within families is a major barrier. "
Monogenic etiologies of persistent human papillomavirus infections: a comprehensive systematic review
S Biglari et al, Genetics in Medicine, November 2023
(Posted: Nov 17, 2023 8AM)
From the abstract: " Persistent human papillomavirus infection (PHPVI) causes cutaneous, anogenital, and mucosal warts. Cutaneous warts include common warts, Treeman syndrome, and epidermodysplasia verruciformis, among others. Although more reports of monogenic predisposition to PHPVI have been published with the development of genomic technologies, genetic testing is rarely incorporated into clinical assessments. In this systematic review, we found that PHPVI has at least 83 monogenic etiologies and a genetic diagnosis is essential for effective management."
Modernizing Federal Oversight of Laboratory-Developed Tests - Toward Safety, Validity, and Utility.
Udit Singhal et al. N Engl J Med 2023 11 (19) 1735-1737
(Posted: Nov 09, 2023 2PM)
From the paper: "Advances in precision medicine have fueled an evolution in the availability of laboratory-developed tests (LDTs). Defined as in vitro diagnostic tests that are “designed, manufactured, and used in a single laboratory,” LDTs were initially conceived as simple tests offered to limited, local groups of patients.1 But LDTs have grown in complexity, and some hospital and commercial laboratories now accept specimens from around the world. "
Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing.
Elaine Chen et al. JAMA Netw Open 2023 10 (10) e2339571
(Posted: Oct 27, 2023 9AM)
From the abstract: " How are variants of uncertain significance (VUSs) distributed across genetic disorders and what evidence contributes to their resolution?
In this cohort study of 1?689?845 individuals who predominantly underwent multigene panel testing, 41% had VUSs (mostly missense changes), most often among those who underwent testing for disorders with incomplete penetrance or were identified as Asian or Shephardic Jewish individuals. Among unique VUSs, 7.3% were reclassified, with most reclassified as benign, often using clinical and experimental evidence."
Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples
R Wyngaard et al, EJHG, October 19, 2023
(Posted: Oct 19, 2023 2PM)
From the abstract: "Mobile element insertions (MEIs) are a known cause of genetic disease but have been underexplored due to technical limitations of genetic testing methods. Various bioinformatic tools have been developed to identify MEIs in Next Generation Sequencing data. However, most tools have been developed specifically for genome sequencing (GS) data rather than exome sequencing (ES) data, which remains more widely used for routine diagnostic testing. "
Factors associated with adherence to BRCA1/2 mutation testing after oncogenetic counseling in long-surviving patients with a previous diagnosis of breast or ovarian cancer.
Silvia Actis et al. J Community Genet 2023 9
(Posted: Sep 21, 2023 2PM)
From the abstract: "We analyzed socio-demographic and psychological parameters associated with the decision to undergo BRCA1/2 genetic testing or the reasons behind the withdrawal. Thirty-nine patients underwent BRCA1/2 genetic testing. Patients who accept the genetic test communicate more easily with family members than those who refuse. Factors associated with test refusal are having a long-term partner and having a negative perception of life. There is a trend, although not statistically significant, toward younger age at cancer diagnosis, more likely to participate in cancer screening programs (71.8% vs. 45.5%), and more likely to have daughters (63.3% vs. 37.5%) in the group that accepted the test. "
An Environmental Scan of Consumer-Initiated Germline Genetic Testing for Health Risks.
Hannah G Kirby et al. Mayo Clin Proc 2023 8
(Posted: Aug 29, 2023 11AM)
From the abstract: "An environmental scan was conducted to identify germline genetic testing companies that offer testing for at least one diagnosable health condition and are available for purchase by consumers in the US market without a visit to one's health care provider. We characterized variability in the content and processes used by 21 companies offering 74 distinct test products that met our inclusion and exclusion criteria. A minority (8 of 21 companies) offered tests that assessed the presence of at least 1 US Centers for Disease Control and Prevention Tier 1 condition for which detection can impact an individual's clinical care and for which evidence-based guidelines for detection and management exist."
Genome sequencing for the fast diagnosis of early-onset epilepsies.
Katrine M Johannesen et al. Lancet Neurol 2023 8 (9) 773-774
(Posted: Aug 23, 2023 10AM)
From the paper: "Technological advances have enabled genetic testing to become the first-line diagnostic investigation for individuals with early-onset epilepsies. A precise genetic diagnosis is essential because it has both personal and clinical utility and might enable timely administration of targeted treatments."
Beyond the exome: What's next in diagnostic testing for Mendelian conditions.
Monica H Wojcik et al. Am J Hum Genet 2023 8 (8) 1229-1248
(Posted: Aug 15, 2023 2PM)
Despite advances in clinical genetic testing, including the introduction of exome sequencing (ES), more than 50% of individuals with a suspected Mendelian condition lack a precise molecular diagnosis. Clinical evaluation is increasingly undertaken by specialists outside of clinical genetics, often occurring in a tiered fashion and typically ending after ES. The current diagnostic rate reflects multiple factors, including technical limitations, incomplete understanding of variant pathogenicity, missing genotype-phenotype associations, complex gene-environment interactions, and reporting differences between clinical labs.
Genetic testing and other healthcare use by Black and white individuals in a genomic sequencing study.
Katherine W Saylor et al. Public Health Genomics 2023 8
(Posted: Aug 14, 2023 1PM)
We assessed factors associated with the odds of having ever received genetic testing prior to enrollment in a genomic sequencing study among 674 self-identified white and 407 self-identified African, African American, or Afro-Caribbean (“Black”) individuals. Controlling for individual determinants of healthcare use (demographics, personality traits, knowledge and attitudes, and health status), identifying as Black was associated with lower odds of prior genetic testing (OR = 0.43, 95% CI [0.27-0.68], p<0.001). In contrast, self-identified race was not associated with the use of non-genetic clinical screening tests.
Why don’t we all use genomic testing?
A McNeill, EJHG, August 9, 2023
(Posted: Aug 09, 2023 4PM)
Genomic testing is vital for the diagnosis of many rare conditions. However, globally, there is not equity of access to such technologies. Lack of funding is a major barrier. However, Mordaunt et al. found that even when fully funded, uptake of genome sequencing for intellectual disability was less than expected [1]. They suggest that allowing mainstream clinicians to order testing may increase uptake.
The landscape of reported VUS in multi-gene panel and genomic testing: Time for a change
HL Rehm et al, Genetics in Medicine, July 30, 2023
(Posted: Jul 31, 2023 11AM)
Variants of uncertain significance (VUS) are a common result of diagnostic genetic testing and can be difficult to manage with potential misinterpretation and downstream costs, including time investment by clinicians. We investigated the rate of VUS reported on diagnostic testing via multi-gene panels (MGPs) and exome and genome sequencing (ES/GS) to measure the magnitude of uncertain results and explore ways to reduce their potentially detrimental impact.
Universal genetic testing may improve risk stratification and treatment for rare and lethal cancer
L Ramsey, News Medical, July 27, 2023
(Posted: Jul 30, 2023 10AM)
Esophageal adenocarcinoma (EAC) is a highly lethal cancer, with a five-year survival rate of less than 20 percent. Although a precursor lesion to EAC, called Barrett's esophagus (BE), is present in roughly seven percent of middle-aged adults, less than one percent of BE patients will progress to EAC, making it difficult to determine which individuals are at risk of developing this deadly cancer. To better understand why only a small fraction of individuals with BE develop EAC, investigators used genomic databases to identify genetic drivers associated with EAC. The found that nine percent of EAC patients harbor mutations in cancer-predisposing genes, shedding light on the causes of progression to the disease and new possibilities for screening and treatment.
Special Issue: “Genetic Counseling and Genetic Testing in Precision Medicine”
E Turbitt et al, J Per Med, July 27, 2023
(Posted: Jul 27, 2023 7AM)
Delivering on the promises of precision medicine comprehensively, equitably, and promptly depends on optimizing health service delivery to facilitate access to timely, evidence-based genetic and genomic testing. Improvements in access to genetic counseling and testing enable the delivery of the ‘right care to the right patient at the right time’. This Special Issue of the Journal of Personalized Medicine showcases the latest research on genetic counseling and genetic testing in precision medicine.
Too many treatable diseases go unnoticed. This could change that.
B Venkataraman, Washington Post, July 26, 2023
(Posted: Jul 27, 2023 7AM)
Hundreds of treatable genetic diseases go unnoticed for years — not because they cannot be diagnosed, but because newborn screening for them is not routine in the United States. If biomedical breakthroughs are to benefit the millions of children afflicted with rare diseases, genetic testing of babies needs to expand. This is an urgent problem for families now, but its solution could also pave the way for a future in which doctors can treat many more rare, intractable diseases. By screening newborn genomes for currently known genetic diseases, patients and scientists could gain insights that lead to the treatment and prevention of thousands of illnesses that currently lack cures.
Persistent Underutilization of BRCA Testing for Breast and Ovarian Cancer in the United States: Implications for Health Disparities
L Shi et al, CDC Blog Post, July 25, 2023
(Posted: Jul 25, 2023 11AM)
Two recent studies document ongoing underutilization and disparities in genetic testing for patients with breast and ovarian cancer. The two studies demonstrate the importance of population-level data to track progress in implementation, outcomes, and disparities in genomic medicine. The studies also show how diverse data sources, such as state-based cancer registries, laboratory, EHR, administrative claims, and survey data, each with its own strengths and limitations, can be used to help build the evidence base on genetic testing utilization and disparities.
Public attitudes challenge clinical practice on genetic risk disclosure in favour of healthcare-provided direct dissemination to relatives
A Rosen et al, EJHG, July 20, 2023
(Posted: Jul 20, 2023 7AM)
Germline genetic testing often has implications not only for the individual patient but also for their genetic relatives. This is especially true for high-penetrance pathogenic variants associated with conditions such as familial hypercholesterolemia and hereditary cancer risk syndromes like Lynch syndrome and the hereditary breast and ovarian cancer syndrome. For these conditions, targeted prevention programs are available, and cascade screening is cost-effective. It is therefore highly relevant to find effective strategies to disclose information from the genetic investigation to healthy relatives at risk. Informing relatives at risk enables equitable access to pre-test genetic counselling and a possibility for them to make an informed decision about genetic testing as well as prevention.
Germline pathogenic variants in metaplastic breast cancer patients and the emerging role of the BRCA1 gene
G Corso et al, EJHG, July 18, 2023
(Posted: Jul 18, 2023 2PM)
we retrospectively reviewed all BC patients counseled at our Institute for genetic testing of at least BRCA1 or BRCA2 (BRCA) genes and we found that 23 (23/5226?=?0.4%) were affected by MpBC. About 65% (15/23) of MpBC patients harbored a germline pathogenic variant (PV): 13 in BRCA1 (86.7%), including two patients who received genetic testing for known familial PV, one in TP53 (6.7%), and one in MLH1 (6.7%). Our results confirmed that BRCA1 is involved in MpBC predisposition.
Genomic Sequencing for Ill Newborns
JAMA Network Learning Podcast July 2023
(Posted: Jul 17, 2023 8AM)
The performance of whole-genome sequencing in comparison with targeted genomic testing methods is not well understood. In this podcast, JAMA Associate Editor W. Gregory Feero, MD, PHD, interviews author Jill L. Maron, MD, MPH, of the Women and Infants Hospital of Rhode Island about a study of whole-genome sequencing vs a commercially available targeted genetic testing platform for diagnosing ill neonates with suspected genetic conditions.
EMQN: Recommendations for genetic testing in inherited cardiomyopathies and arrhythmias
JB Hayesmoore et al. EJHG July 13, 2023
(Posted: Jul 14, 2023 1PM)
Inherited cardiomyopathies and arrhythmias (ICAs) are a prevalent and clinically heterogeneous group of genetic disorders that are associated with increased risk of sudden cardiac death and heart failure. Making a genetic diagnosis can inform the management of patients and their at-risk relatives and, as such, molecular genetic testing is now considered an integral component of the clinical care pathway. However, ICAs are characterised by high genetic and allelic heterogeneity, incomplete / age-related penetrance, and variable expressivity.
No need for options for choice for unsolicited findings in informed consent for clinical genetic testing
EM Bunnik, EJHGH July 13, 2023
(Posted: Jul 14, 2023 1PM)
Screening during IVF for inherited diseases can greatly reduce costs of care
L Flynn, MedicalXpress, July 2023
(Posted: Jul 10, 2023 7AM)
For prospective parents who are carriers of many inherited diseases, using in vitro fertilization along with genetic testing would significantly lower health care expenditures, according to a new study. Preimplantation genetic diagnostic testing during IVF, or PGD-IVF, is now being used to screen for single-gene defect conditions such as cystic fibrosis, sickle cell disease and Tay-Sachs disease, along with nearly 400 others.
Most people share genetic test results with relatives even if the findings are normal: family communication in a diverse population
JE Hunter et al, Genet Med, July 6, 2023
(Posted: Jul 07, 2023 9AM)
With increasing utilization of genetic testing, sharing genetic information can become part of general family health communication while providing biological relatives with important information about their own genetic risk. Importantly, little is known about motivations for and barriers to family communication of genetic information in historically underserved populations. Most participants overall (91%), including most with normal findings (89%), shared or planned to share their results with relatives. Common motivations for sharing results were to give relatives information about their genetic risk and because the participant thought the results were interesting.
Meeting the need for germline testing
Lancet Oncology editorial, July 2023
(Posted: Jul 05, 2023 7AM)
Germline genetic testing for pathogenic mutations in people diagnosed with cancer is recommended for several cancer types and has been shown to have a positive effect on survival. The US NCCN guidelines recommend that all, or a high proportion of, patients with a personal history of breast, ovarian, endometrial, pancreatic, colorectal, and prostate cancer should undergo germline testing. Yet, in a new study, only 6·8% of patients diagnosed with one of seven cancers in California and Georgia, USA, between 2013 and 2019, underwent genetic testing.
Data for Action in Public Health Genomics: Ensuring Equitable Implementation of Genomic Applications Across the Lifespan
MJ Khoury et al CDC Blog Post, June 23, 2023
(Posted: Jun 24, 2023 10AM)
Our office is currently identifying gaps in the effective implementation of tier 1 genomic applications. These include the limitations of current public health and healthcare data sources for tracking trends in genetic testing and identifying health disparities and their underlying contributors. These data are needed more than ever to drive practice, programs, and policy, to fulfill the promise of genomics to improve population health and to reduce health inequities.
ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG)
DT Miller et al, Genetics in Medicine, June 22, 2023
(Posted: Jun 22, 2023 7AM)
The American College of Medical Genetics and Genomics (ACMG) previously published guidance for reporting secondary findings (SFs) in the context of clinical exome and genome sequencing. The ACMG Secondary Findings Working Group (SFWG) and Board of Directors (BODs) have agreed that the list of recommended genes should now be updated annually, but with an ongoing goal of maintaining this as a minimum list. Reporting of SFs should be considered neither a replacement for indication-based diagnostic clinical genetic testing nor a form of population screening.
Interventions to support patients with sharing genetic test results with at-risk relatives: a synthesis without meta-analysis (SWiM)
LM Ballard et al, EJHG, June 21, 2023
(Posted: Jun 21, 2023 7AM)
Whilst the finding of heritable susceptibility to disease was once relatively rare, mainstreaming of genetic testing has resulted in a steady increase. Patients are often encouraged to share their genetic test results with relevant relatives, but relatives may not receive this information, leaving them without knowledge of their own risk. Therefore, strategies to help communicate such information are important. This review aimed to explore the efficacy of existing interventions to improve the sharing of genetic test results.
Assessing the general public's view of direct-to-consumer (DTC) genetic testing and their interpretation of DTC website disclaimer messages.
Madison Ruehl et al. Eur J Hum Genet 2023 6
(Posted: Jun 20, 2023 7AM)
The general public continues to show increased interest and uptake of Direct-to-Consumer (DTC) genetic testing. We conducted an online survey (N?=?405) to assess genetics knowledge, interest, and outcome expectancy of DTC genetic testing before and after exposure to a sample DTC disclaimer message.
Increased genetic knowledge and more positive attitudes towards DTC genetic testing were associated with increased self-reported systematic processing of the DTC disclaimer message. Further, self-reported systematic processing of the DTC disclaimer message was associated with greater interest in pursuing DTC genetic testing but did not predict outcome expectancies.
International genetic counseling: What do genetic counselors actually do?
K Ormond et al, J Genetic Counseling, June 2023
(Posted: Jun 12, 2023 9AM)
Twenty activities were identified as common (=74%) across multiple countries, encompassing most subcategories of genetic counseling activity. Activities with most frequent endorsement include: reviewing referrals and medical records and identifying genetic testing options as part of case preparation; taking family and medical histories; performing and sharing risk assessment; and educating clients about basic genetic information, test options, outcomes and implications, including management recommendations on the basis of the test results.
What matters to parents? A scoping review of parents’ service experiences and needs regarding genetic testing for rare diseases
E Crellin et al, EJHG, June 12, 2023
(Posted: Jun 12, 2023 9AM)
To understand parents’ service experiences and needs regarding testing of their child for rare diseases, we conducted a scoping review. Five databases were searched (2000–2022), with 29 studies meeting the inclusion criteria. Parents especially valued and emphasised the importance of feeling ‘cared for’, continuous relationships with clinicians, empathic communication, being kept informed while awaiting genetic test results, linkage with informational and psychosocial resources following results disclosure, and follow-up.
Defining critical educational components of informed consent for genetic testing: views of US-based genetic counselors and medical geneticists
MLG Hallquist et al, EJHG, June 12, 2023
(Posted: Jun 12, 2023 9AM)
The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendation (CADRe) framework proposes that key components of informed consent for genetic testing can be covered with a targeted discussion for many conditions rather than a time-intensive traditional genetic counseling approach. We surveyed US genetics professionals (medical geneticists and genetic counselors) on their response to scenarios that proposed core informed consent concepts for clinical genetic testing.
Providing Genetic Testing and Genetic Counseling for Parkinson’s Disease to the Community
L Cook et al, Genetics in Medicine, June 8, 2023
(Posted: Jun 09, 2023 8AM)
A multicenter, exploratory pilot study at seven academic hospital sites in the United States tracked enrollment and randomized participants to receive results and genetic counseling at local sites or by genetic counselors, remotely. Follow-up surveys measured participant/provider satisfaction, knowledge, and psychological impact.
Germline Genetic Testing After Cancer Diagnosis.
Allison W Kurian et al. JAMA 2023 6
(Posted: Jun 06, 2023 8AM)
Among patients in the Surveillance, Epidemiology, and End Results registries diagnosed with cancer between 2013 and 2019, what was the prevalence of germline genetic testing? In this observational study that included 1?369?602 patients diagnosed with cancer in California and Georgia, germline genetic testing after cancer diagnosis was low (6.8%; n?=?93?052). Testing was highest in males with breast cancer (50%) and in patients with ovarian cancer (38.6%). Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.
Genetic Testing for Cancer Susceptibility.
Zsofia K Stadler et al. JAMA 2023 6
(Posted: Jun 06, 2023 8AM)
In patients diagnosed with cancer, testing for gene variants associated with increased cancer susceptibility is important for at least 2 reasons. First, testing informs the most optimal treatment for a patient with cancer. Second, testing helps identify relatives who may have inherited genes that increase their cancer susceptibility. Identifying these genes could improve outcomes by increasing cancer screening and risk-reducing measures such as preventive surgery. With the advent of next-generation sequencing technologies, genetic testing for cancer risk has shifted from sequential, single-gene testing to multiple-panel genetic testing using blood or saliva.
Direct-to-Consumer Genetic Testing
NHGRI, June 2023
(Posted: Jun 05, 2023 10AM)
The Direct-to-Consumer Genetic Testing (DTC-GT) Project Group of the Inter-Society Coordinating Committee for Practitioner Education in Genomics has created a DTC-GT Frequently Asked Questions (FAQ) resource designed for the general clinician who may see patients requesting guidance on DTC-GT. This FAQ is intended to help healthcare professionals understand the diverse landscape of DTC-GT, the benefits and limitations of these tests and how results of DTC-GT may affect their patients’ health, wellness and medical decision making.
Genetic Counseling Under the Microscope: Expanding the Scope of the Profession through Research Initiatives and Educational Opportunities
J Goehringer, NSGC, June 2023
(Posted: Jun 04, 2023 2PM)
Geisinger initiated a population health genomic screening program in 2007, now known as the MyCode Community Health Initiative. Adults and children (with or without personal or family history of genetic disease) have received genetic testing results through this program. Numerous qualitative research projects have stemmed from MyCode, which have improved our understanding of these lived experiences.
Barriers to Genetic Testing in Vascular Malformations
AJ Borst et al, JAMA Network Open, May 23, 2023
(Posted: May 23, 2023 2PM)
What are the barriers to obtaining genetic information for patients with vascular malformation (VM)? In this survey study of 55 vascular anomaly specialists (primarily pediatric hematologists-oncologists), barriers to genetic testing for VM were identified across vascular anomaly centers of all sizes, including lack of administrative support; unclear institutional, insurance, and laboratory requirements; and lack of clinician education.
Genetic testing in monogenic early-onset atrial fibrillation.
Brandon Chalazan et al. Eur J Hum Genet 2023 5
(Posted: May 23, 2023 11AM)
We aim to determine the prevalence of likely pathogenic and pathogenic variants from AF genes with robust evidence in a well phenotyped early-onset AF population. We performed whole exome sequencing on 200 early-onset AF patients. Variants from exome sequencing in affected individuals were filtered in a multi-step process, prior to undergoing clinical classification using current ACMG/AMP guidelines. There was a 3.0% diagnostic yield for identifying a likely pathogenic or pathogenic variant across AF genes with robust gene-to-disease association evidence.
Haemochromatosis.
Paul C Adams et al. Lancet 2023 4
(Posted: May 21, 2023 3PM)
Haemochromatosis is one of the most common genetic diseases affecting patients of northern European ancestry. It is overdiagnosed in patients without iron overload and is underdiagnosed in many patients. Early diagnosis by genetic testing and therapy by periodic phlebotomy can prevent the most serious complications, which include liver cirrhosis, liver cancer, and death.
Information-Seeking Preferences in Diverse Patients Receiving a Genetic Testing Result in the Clinical Sequencing Evidence-Generating Research (CSER) Study
A Slavotinek et al, Genetics in Medicine, May 19, 2023
(Posted: May 19, 2023 2PM)
Accurate and understandable information following genetic testing is critical for patients, family members, and professionals alike. As part of a cross-site study from the Clinical Sequencing Evidence-Generating Research (CSER) consortium, we investigated the information-seeking practices among patients and family members at five to seven months after genetic testing results disclosure, assessing the perceived utility of a variety of information sources, such as family and friends, healthcare providers, support groups, and the internet.
Diagnostic and prognostic relevance of using large gene panels in the genetic testing of patients with dilated cardiomyopathy.
Sophie L V M Stroeks et al. Eur J Hum Genet 2023 5
(Posted: May 19, 2023 10AM)
It was previously suggested that increasing the number of genes on diagnostic gene panels could increase the genetic yield in patient with dilated cardiomyopathy (DCM). We explored the diagnostic and prognostic relevance of testing DCM patients with an expanded gene panel. The current study included 225 consecutive DCM patients who had no genetic diagnosis after a 48-gene cardiomyopathy-panel. Overall, the use of large gene panels for genetic testing in DCM does not increase the diagnostic yield. Current diagnostic gene panels should be limited to the robust DCM-associated genes.
Who is Involved in Public Health Genetics and Genomics?
PHGW, May 2023
(Posted: May 17, 2023 11AM)
The public health genetics and genomics system make up many organizations and individuals that work together to deliver genetic services, including genetic testing and counseling, and ensure access to genetic services for a population. Below, you can find more information about the various roles of individuals within the public health system, as well as organizations that contribute to the system.
Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients
J Henkel et al, AJHG, May 16, 2023
(Posted: May 15, 2023 9AM)
A Multicenter Cross-Sectional Study in Infants with Congenital Heart Defects Demonstrates High Diagnostic Yield of Genetic Testing but Variable Evaluation Practices
MD Durbin et al, Genet in Med Open, May 2023
(Posted: May 14, 2023 9AM)
A multicenter cross-sectional study of five large children’s hospitals, including 2899 children = 14 months undergoing surgical repair for CHD in 2013-2016, followed by multivariate logistics regression analysis. Genetic testing occurred in 1607 of 2899 patients (55%). Testing rates differed highly between institutions (42% - 78%, p< 0.001). Choice of testing modality also differed across institutions (i.e., chromosomal microarray, 26% - 67%, p< 0.001). Genetic testing was abnormal in 702 of 1607 patients (44%) and no major phenotypic feature drove diagnostic yield. Only 849 patients were seen by geneticists (29%).
Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients
NA Husn et al, Genetics in Medicine, May 6, 2023
(Posted: May 06, 2023 7AM)
Adoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions. 645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses (P < .001). Yield was greater for GS vs. TGPs in Hispanic/Latino(a) (17.2% vs. 9.5%, P < .001) and White/European American (19.8% vs. 7.9%, P < .001), but not in Black/African American (11.5% vs. 7.7%, P = .22) population groups.
Demographic Characteristics Associated With Perceptions of Personal Utility in Genetic and Genomic Testing: A Systematic Review.
Emily G Miller et al. JAMA Netw Open 2023 5 (5) e2310367
(Posted: May 06, 2023 7AM)
n this systematic review of 52 studies with 13?251 eligible participants, sex or gender was the most frequently reported demographic characteristic, followed by race and ethnicity, education, and income. Participants were disproportionately women or female (71%), White (76%), had a college degree or higher education (65%), and reported income above the US median (67%). These findings suggest that the current literature on the personal utility of genetics and genomics underrepresents the perspectives of individuals with diverse demographic backgrounds.
Offering genetic testing at the point of care may increase uptake
Medical Xpress, May 3, 2023
(Posted: May 05, 2023 10AM)
Genetic testing for hereditary cancers, such as breast, colon, pancreatic, and ovarian cancer, helps at-risk individuals understand their familial risk for these diseases and make informed decisions about next steps in care. But fewer than 20 percent of at-risk patients utilize this testing, and even fewer engage in genetic counseling after referral, often due to clinical workflow challenges or barriers to care. A new study researchers haveidentified a streamlined approach in clinical settings that may help advance these efforts by simplifying the process of identifying hereditary cancer risk and determining subsequent care.
Evaluating cancer genetic services in a safety net system: overcoming barriers for a lasting impact beyond the CHARM research project
S Okuyama et al, J Comm Genetics, May 1, 2023
(Posted: May 02, 2023 8AM)
The Cancer Health Assessments Reaching Many (CHARM) study evaluated ways to increase access to genetic testing for individuals in underserved populations at risk for hereditary cancer syndromes (HCS). Here, we report the successful implementation of CHARM in a low-resource environment and the development of sustainable processes to continue genetic risk assessment in this setting. Through iterative and collaborative stakeholder engagement, the team identified barriers and developed solutions that would both facilitate participation in CHARM and be feasible to implement and sustain long term in clinical care.
‘The human genome revealed its secrets 20 years ago. It’s time to fulfill its promise of personalized health care’
A Wojicki, Fortune Magazine, April 25, 2023
(Posted: Apr 29, 2023 3PM)
Sequencing the human genome for the first time was an incredible feat. Twenty years ago this week, the sequencing project was completed with the promise that it would transform how we predict, prevent, and treat almost all human disease. With such an important discovery under our belt, one would believe we are now on the cusp of a new phase in personalized healthcare, one that uses genetics to inform every patient journey. Yet, we are still far from the delivery of personalized healthcare for everyone. The problem is not a lack of scientific progress, but rather a failure to implement widespread genetic testing and personalized medicine for all who could benefit from it.
Underrepresentation of racial and ethnic minorities in cascade testing for hereditary cancer syndromes
MD Ahsan et al, EJHG, April 28, 2023
(Posted: Apr 28, 2023 8AM)
Mathematical modeling suggests that the combination of germline genetic testing at time of cancer diagnosis with subsequent cascade testing of at-risk relatives has the potential to identify all individuals with a cancer predisposing pathogenic variant in the United States in less than a decade [4]. However, our recent systematic review demonstrates that only about a third of at-risk relatives undergo recommended cascade testing.
'It Totally Backfired': The Pitfalls of Alzheimer's Genetic Testing
J Steenhuysen, Medscape, April 24, 2023
(Posted: Apr 25, 2023 7AM)
Testing for the APOE4 gene variant among Americans being treated for Alzheimer's has more than doubled from a year ago. The increase was driven by the new treatments that promise to slow the progression of the disease, but also carry risks, especially for people like Nelson carrying two copies of APOE4. Yet few support services are available to help people deal with the implications of APOE4 testing, according to interviews with more than a dozen neurologists and genetic counselors.
Clinical, technical, and environmental biases influencing equitable access to clinical genetics/genomics testing: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG)
DR Matalon et al, Genetics in Medicine, April 14, 2023
(Posted: Apr 14, 2023 9AM)
As genetic testing becomes increasingly endorsed by the medical community and available to the public, a working group formed by members of the Social, Ethical and Legal Issues and Diversity, Equity and Inclusion committees of the American College of Medical Genetics and Genomics (ACMG) developed this document in an effort to address current factors in which bias can occur in clinical genetic testing and within the medical genetics profession, with the goal of fostering awareness and identifying strategies to reduce bias and improve health equity.
Why genetic testing should always be offered to children with neurodevelopmental differences
D Ondrasick, Stat News, April 10., 2023
(Posted: Apr 11, 2023 0PM)
As a board-certified pediatrician and the mother of a child with a rare disease, I believe the medical system is failing the rare disease community by vastly underdiagnosing genetic disorders. Most families are offered either no genetic testing at all or only limited panels that cannot find most genetic mutations. Given the benefits I have seen for my family and my patients, I urge the AAP to develop new guidelines that are aligned with the 2021 American College of Medical Genetics and Genomics practice guidelines. These recommend whole exome/genome sequencing as a first or second-tier test for pediatric patients with congenital anomalies, developmental delay, or intellectual disability.
Trends in Availability of Genetic Tests in the United States, 2012–2022
AL Halbisen et al, J Per Med, April 5, 2023
(Posted: Apr 06, 2023 0PM)
Using publicly available data from the Genetic Testing Registry, we analyzed trends in the availability of genetic tests in the United States over the last decade. As of November 2022, a total of 129,624 and 197,779 genetic tests in the US and globally, respectively, including updated versions of previously existing tests, have been made available and submitted to the genetic testing registry. Over 90% of tests submitted to GTR are for clinical rather than research purposes. Worldwide, 1081 and 6214 new genetic tests had been made available in 2012 and in 2022, respectively. In 2012, only 607 and in 2022, 3097 new genetic tests were made available in the US, with 2016 seeing the biggest increase in availability of new tests during the study period.
Genetic Testing in Patients With Congenital Heart Disease: You Do No Harm When Using the Right Tools!
Julie De Backer et al. Circulation. Genomic and precision medicine 2023 3 e004104
(Posted: Mar 31, 2023 6AM)
Polygenic Scores in the Direct-to-Consumer Setting: Challenges and Opportunities for a New Era in Consumer Genetic Testing
JK Park et al, J Per Med, March 23, 2023
(Posted: Mar 23, 2023 7AM)
While PGS have thus far been extensively explored as clinical and public health tools, the use of PGS in consumer genetic testing has not yet received systematic attention, even though they are already in use for some consumer genetic tests. In this narrative review, we highlight the ethical, legal, and social implications of the use of PGS in DTC genetic tests and synthesize existing solutions to these concerns.
Equity implications of patient-initiated recontact and follow-up in clinical genetics
MP Mackley et al, EJHG, March 23, 2023
(Posted: Mar 23, 2023 6AM)
Moving forward, as policies and practices are updated, the equity implications of a shared model of responsibility in recontact (and follow-up) must be carefully considered. As it stands, the aspirational shared model is not shared equally: patients are driving recontact in clinical genetics. As a result, there is a disconnect between the potential for recontact—if systematic—to promote equity in genetic testing and the inconsistent patient-initiated product.
Limitations, concerns and potential: attitudes of healthcare professionals toward preimplantation genetic testing using polygenic risk scores
M Siermann et al, EJHG, March 20, 2023
(Posted: Mar 21, 2023 9AM)
We found that most healthcare professionals were concerned about the prematurity of introducing PGT-P into clinical practice. They had various ethical considerations, such as concerns related to validity and utility of PGT-P, limited embryos and options, and difficulties for prospective parents regarding comprehension and informed decision-making. Positive aspects were also identified, e.g., regarding reproductive autonomy and potential health benefits. Overall, most healthcare professionals considered that clinical implementation of PGT-P is premature.
Communicating risk and the landscape of cancer prevention - an exploratory study that examines perceptions of cancer-related genetic counseling and testing among African Americans and Latinos in the Midwest.
Crystal Y Lumpkins et al. Journal of community genetics 2023 3 1-13
(Posted: Mar 20, 2023 7AM)
Six focus groups were held with a pilot sample of African Americans and Latinos who self-reported to be at-risk for cancer (N?=?53). Themes that emerged included (1) the lack of knowledge about cancer-related genetic counseling and testing; (2) cancer is feared often; (3) cancer-related genetic testing was perceived as something that could help but was also perceived as unnecessary testing that exposed individuals to medical harm; and (4) benefits to test were perceived as favorable for medical personnel but not for the patient.
Implications of Genomic Newborn Screening for Infant Mortality
MH Wojick et al, IJNS, March 2023
(Posted: Mar 09, 2023 1PM)
Current diagnostic genetic workflows are designed to initiate genetic testing after an infant develops disease symptoms, at which time therapies may not be clinically useful. There is increasing interest and an international effort to incorporate genome-wide sequencing into newborn screening approaches, though ethical considerations and other implementation concerns remain unresolved. Here, we comment on the implications of this approach for infant mortality reduction.
Detection of subclinical hypertrophic cardiomyopathy.
George Joy et al. Nature reviews. Cardiology 2023 3
(Posted: Mar 09, 2023 1PM)
Hypertrophic cardiomyopathy (HCM) is defined by ventricular hypertrophy. However, the broader phenotype includes abnormal cardiomyocyte orientation (disarray), myocardial ischaemia and electrical abnormalities, which seem to manifest before overt hypertrophy. With advances in cascade genetic testing and novel therapeutic agents, the detection of subclinical HCM is a rapidly emerging priority. In this context, we outline the role of novel biomarkers, particularly quantitative perfusion and diffusion tensor MRI.
Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines: A Systematic Review and Meta-analysis.
Pedro J Gonzalez-Mantilla et al. JAMA pediatrics 2023 3
(Posted: Mar 07, 2023 6PM)
Is the diagnostic yield of exome or genome sequencing in cerebral palsy similar to that of other neurodevelopmental disorders for which exome sequencing is recommended as a first-tier clinical diagnostic test? In this systematic review and meta-analysis that included 13 studies and 2612 individuals with cerebral palsy, the diagnostic yield of exome or genome sequencing was 31.1%, which is similar to that of other neurodevelopmental disorders, regardless of comorbid intellectual disability/developmental delay.
Human-centered design study to inform traceback cascade genetic testing programs at three integrated health systems
KM Romagnoli et al, Public Health Genomics, March 2023
(Posted: Mar 04, 2023 8AM)
We interviewed 70 participants and identified five preferred experiences for a traceback program. Participants strongly prefer discussing genetic testing with their doctor but are comfortable discussing with other clinicians. The most highly preferred experience for both probands and relatives was to discuss with a knowledgeable clinician who can answer questions, followed by directed (sent directly to specific people) or passive (shared in a public area) communication. Repeated contact was acceptable for reminders.
Approaches to Genetic Screening in Cardiomyopathies: Practical Guidance for Clinicians.
Amy R Kontorovich et al. JACC. Heart failure 2023 2 (2) 133-142
(Posted: Mar 01, 2023 0PM)
Patients and families benefit when the genetic etiology of cardiomyopathy is elucidated through a multidisciplinary approach including genetic counseling and judicious use of genetic testing. The yield of genetic testing is optimized when performed on a proband with a clear phenotype, and interrogates genes that are validated in association with that specific form of cardiomyopathy. Variants of uncertain significance are frequently uncovered and should not be overinterpreted.
How Can Implementation Science Improve the Care of Familial Hypercholesterolaemia?
Mitchell Sarkies et al. Current atherosclerosis reports 2023 2
(Posted: Feb 25, 2023 6AM)
Gaps between evidence and practice, such as underutilization of genetic testing, family cascade testing, failure to achieve LDL-cholesterol goals and low levels of knowledge and awareness, have been identified through clinical registry analyses and clinician surveys. Implementation science theories, models and frameworks have been applied to assess barriers and enablers in the literature specific to local contextual factors (e.g. stages of life).
Implementation of Population-Based Genetic Testing of Newborn Infants for Prediction of Hearing Loss in Ontario, Canada
CDC Webinar, April 19, 2023
(Posted: Feb 22, 2023 6AM)
In 2019, Newborn Screening Ontario launched a novel screening approach for genetic permanent hearing loss (PHL) risk involving universal testing of newborn dried blood spots for a panel of penetrant GJB2 and SLC26A4 variants associated with congenital or very early onset PHL. In July 2020, the less penetrant and relatively frequent GJB2 V37I variant was added to the panel. Babies homozygous for this variant, or heterozygous for this variant and a penetrant variant, are estimated to be at ~20% risk for congenital hearing loss and ~50% risk of developing moderate or more severe PHL by age 5.
Points to consider in the practice of postmortem genetic testing: A statement of the American College of Medical Genetics and Genomics (ACMG)
JL Deignan et al, Genetics in Medicine, February 16, 2023
(Posted: Feb 17, 2023 7AM)
Next-generation sequencing methods can also be used to more fully characterize a variety of conditions identified at autopsy that are suspected of having a heritable cause. For specific clinical indications such as sudden arrhythmic death syndrome, postmortem genetic testing has a relatively high diagnostic yield.
As “molecular autopsies” involving postmortem genetic testing become more common, there is a need to address the unique set of challenges and issues inherent in postmortem testing.
Diagnostic yield of genetic screening in a diverse, community-ascertained cohort
N Rao et al, MEDRXIV, December 2022
(Posted: Feb 13, 2023 2PM)
Overall, 40,857 people were invited and 2,899 (7.1%) enrolled. Enrollment varied across race and ethnicity groups, with the lowest enrollment among African American individuals (3.3%) and the highest among Multiracial or Other Race individuals (13.0%). Of 2,864 enrollees who received screening results, 106 actionable variants were identified in 103 individuals (3.6%). Of those who screened positive, 30.1% already knew about their results from prior genetic testing. The diagnostic yield was 74 new, actionable genetic findings (2.6%).
Economic evaluation of population-based expanded reproductive carrier screening for genetic diseases in Australia
D Schofield et al, Genetics in Medicine, February 12, 2023
(Posted: Feb 13, 2023 7AM)
Expanded RCS was cost-saving compared with no population screening and cost-effective compared to the three-condition screening (ICER of $6,287 per QALY gained) at an uptake rate of 50% for RCS, 59% for IVF and preimplantation genetic testing, 90% for prenatal diagnosis testing and 50% for elective termination of affected pregnancies and a cost of A$595 per couple screened.
Implementing digital systems to facilitate genetic testing for hereditary cancer syndromes: An observational study of four clinical workflows
C Wang et al, Genetics in Medicine, February 10, 2023
(Posted: Feb 11, 2023 0PM)
This study examined the uptake of genetic counseling and testing following the use of a digital cancer genetic risk assessment program, implemented at 27 health care sites in 10 States using one of four clinical workflows: 1) traditional referral, 2) point-of-care scheduling (POC-S), 3) point-of care counseling/telegenetics (POC-C), and 4) point-of-care testing (POC-T). In 2019, 102,542 patients were screened and 33,113 (32%) were identified as high risk and meeting National Comprehensive Cancer Network (NCCN) genetic testing criteria for Hereditary Breast and Ovarian Cancer, Lynch syndrome or both. Among those identified at high risk, 5147 (16%) proceeded with genetic testing. Genetic counseling uptake was 11% among sites with workflows that included seeing a genetic counselor prior to testing.
Practical Considerations for Reinterpretation of Individual Genetic Variants
PS Applebaum et al, Genetics in Medicine, February 6, 2023
(Posted: Feb 06, 2023 9AM)
With the growing use of genetic testing in medicine, the question of when genetic findings should be reinterpreted in light of new data has become inescapable. The generation of population and disease-specific data, development of computational tools, and new understandings of the relationship of specific genes to disorders can all trigger changes in variant classification that may have important implications for patients and the clinicians caring for them. This is a particular concern for patients from groups underrepresented in current reference datasets, since they have higher rates of uncertain findings.
Assessment of Cancer Predisposition Syndromes in a National Cohort of Children With a Neoplasm.
Jette J Bakhuizen et al. JAMA network open 2023 2 (2) e2254157
(Posted: Feb 04, 2023 7AM)
What is the diagnostic yield of phenotype-driven genetic testing in children with cancer? In this unselected cohort study of 824 Dutch children with a neoplasm, a cancer predisposition syndrome was found in 71 patients (8.6%), of which most (96%) were identified by a phenotype-driven approach.
Proactive Variant Effect Mapping Aids Diagnosis in Pediatric Cardiac Arrest.
Brendan J Floyd et al. Circulation. Genomic and precision medicine 2023 1
(Posted: Jan 31, 2023 8AM)
Exploring Autistic adults' perspectives on genetic testing for autism.
Byres Loryn et al. Genetics in medicine : official journal of the American College of Medical Genetics 2023 1 100021
(Posted: Jan 22, 2023 8AM)
In total 461 respondents completed the survey: while 27% would have wanted genetic testing during childhood, 74% felt that it should only be offered if the Autistic individual is able to consent and 49% felt that genetic testing for autism should not be done at all. Additional work is required to bridge the divide between the Autistic community and health care providers and families to identify if and when genetic testing should be offered.
Association of Genetic Diagnoses of Childhood-Onset Hearing Loss With Cochlear Implant Outcomes.
Carlson Ryan J et al. JAMA otolaryngology-- head & neck surgery 2023 1
(Posted: Jan 18, 2023 1PM)
n this cross-sectional study of 449 children with SNHL, genomic sequencing identified a genetic cause of SNHL for more than 50% of affected children, with 43 genes involved. Cochlear implants were successful in all participants who underwent implant, but children with hearing loss due to deafness-causing alleles of TMPRSS3 and MITF had the best results on speech performance tests. The results suggest that genetic testing is a valuable prognostic tool for managing pediatric hearing loss and a predictor for cochlear implant outcomes.
Medullary Thyroid Carcinoma and Population Screening-The Promise and Pitfalls of Genetic Testing.
Davies Louise et al. JAMA otolaryngology-- head & neck surgery 2023 1
(Posted: Jan 11, 2023 6AM)
Geisinger invited its members to consent to whole-exome sequencing and linked the findings with electronic health record information to identify future targets for medication development and other interventions to improve population health. Patients would be notified through a specifically established MyCode counseling program if they were found to have known, actionable genetic variants. The program has been popular; more than 270?000 Geisinger members have now signed up. The expected rate of actionable variants is approximately 3.5%. The popularity of the program suggests that as broader testing begins to penetrate US health care outside of specialized programs like the Geisinger one, we can expect to see many more patients in our offices who present after having learned they have one of these variants.
The role of genetic testing in diagnosis and care of inherited cardiac conditions in a specialised multidisciplinary clinic
F Stafford et al, Genome Medicine, December 28, 2022
(Posted: Dec 29, 2022 11AM)
The diagnostic yield of genetic testing for inherited cardiac diseases is up to 40% and is primarily indicated for screening of at-risk relatives. Here, we evaluate the role of genomics in diagnosis and management among consecutive individuals attending a specialized clinic. A total of 888 probands fulfilled the inclusion criteria, and genetic testing identified likely pathogenic or pathogenic (LP/P) variants in 330 individuals (37%) and suspicious variants of uncertain significance (VUS) in 73 (8%).
Newborn genetic testing in the United States and access to needed specialist care, National Survey of Children's Health, 2020: A cross-sectional study.
Wiener R Constance et al. PloS one 2022 17(12) e0279352
(Posted: Dec 23, 2022 5PM)
The purpose of this research is to determine if difficulty receiving specialty care for children with genetic diseases is associated with NST determination of the genetic condition. The research hypothesis is that parents/guardians of children with determination of genetic disease from NST are more likely to report no/slight difficulty accessing specialty care versus parents/guardians of children with genetic diseases whose determination was other than NST. This study has a cross-sectional design with National Survey of Children's Health, 2020 data. Data were analyzed for frequency, Rao Scott Chi square, and logistic regression analyses. Of 833 children with genetic diseases, most parents/guardians reported no/slight difficulty in receiving needed specialty care; however, children whose determination of a genetic condition was other than NST were 4.82 times as likely (95%CI: 1.66, 14.02; p = 0.0040) to have difficulty. In analysis adjusted for sex, race, age, premature birth, and birthweight, the adjusted odds ratio was 6.71 (95% CI:1.91, 23.60 p = 0.0031).
Clinical Cancer and Direct-to-Consumer Genetic Test Result-Sharing Behavior: Findings from HINTS 2020
S Makhnoon et al, J Per Med, December 21, 2022
(Posted: Dec 22, 2022 9AM)
Using nationally representative population-based data collected from the Health Information National Trends Survey, we identified the prevalence and factors associated with genetic test result-sharing behavior for high-risk cancer tests, genetic health risk tests, and ancestry tests. Overall, 68.4% of those who underwent high-risk cancer genetic testing shared their results with FDRs, whereas 89.9% shared with HCP/GCs. Women were nine times more likely than men to share, and those with a personal history of cancer were less likely to share with HCP/GCs. Of those tested for genetic health risk, 66.5% shared with HCP/GCs, 38.7% with FDRs, 66.6% with a spouse/partner, 12.8% with a friend, and 14.1% did not share results with anyone.
