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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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445 hot topic(s) found with the query "Genomic medicine"

Ensuring best practice in genomics education: A scoping review of genomics education needs assessments and evaluations
(Posted: Jul 08, 2024 8AM)

From the abstract: " A health workforce capable of implementing genomic medicine requires effective genomics education. Genomics education interventions developed for health professions over the last two decades, and their impact, are variably described in the literature. To inform an evaluation framework for genomics education, we undertook an exploratory scoping review of published needs assessments for, and/or evaluations of, genomics education interventions for health professionals from 2000 to 2023. "

Written communication of whole genome sequencing results in the NHS Genomic Medicine Service: a multi-centre service evaluation
(Posted: May 29, 2024 9AM)

From the abstract: " Whole genome sequencing (WGS) is being used in diagnostic testing for certain clinical indications within the NHS Genomic Medicine Service (GMS) in England. Letter writing is an integral part of delivering results. However, no national guidelines for writing results from WGS exist. This multi-centre service evaluation used mixed methods to understand the content and readability of letters returning diagnostic, variant of uncertain significance (VUS), and no-finding results to paediatric rare disease patients. "

The acceptability and clinical impact of using polygenic scores for risk-estimation of common cancers in primary care: a systematic review
(Posted: May 24, 2024 9AM)

From the abstract: "A total of 190 papers were identified, 18 of which were eligible for inclusion. A cancer risk-assessment tool incorporating PGS was acceptable to the general practice population and their healthcare providers but major challenges to implementation were identified, including lack of evidence for PGS in non-European ancestry and a need for healthcare provider education in genomic medicine. A PGS cancer risk-assessment had relatively limited impact on psychosocial outcomes and health behaviours. However, for prostate cancer, potential applications for its use in primary care were shown. "

Liminality between direct and family-mediated contact in the communication of genetic information to at-risk relatives.
(Posted: Apr 18, 2024 7AM)

From the article: "Ever since genetic test results have been able to be reported, questions have arisen regarding their implications for genetic relatives. Alongside the proband in whom the initial diagnosis is made, family members often also have an interest in the information. Being informed allows an at-risk relative to consider genetic counseling and testing, and to act in advance to prevent or mitigate future morbidity. Indeed, supporting patients to communicate risk information to their relatives is now considered as a key aspect for maximizing the benefits of genomic medicine. "

Strategies to improve implementation of cascade testing in hereditary cancer syndromes: a systematic review
J Chiang et al, NPJ Genomic Medicine, April 5, 2024 (Posted: Apr 04, 2024 9AM)

From the abstract: " Despite growing efforts targeted at improving cascade testing uptake, current literature continues to reflect poor rates of uptake, typically below 30%. This study aims to systematically review current literature on intervention strategies to improve cascade testing, assess the quality of intervention descriptions and evaluate the implementation outcomes of listed interventions. This systematic review shows that most interventions have demonstrated success in improving cascade testing uptake. Uptake of cascade testing was highest with delivery arrangement (68%). However, the quality of description of interventions and assessment of implementation outcomes are often suboptimal, hindering their replication and implementation downstream."

Secondary use of genomic data: patients’ decisions at point of testing and perspectives to inform international data sharing
M Martyn et al, EJHG, March 25, 2024 (Posted: Mar 25, 2024 8AM)

From the abstract: "International sharing of genomic data files arising from clinical testing of patients is essential to further improve genomic medicine. Whilst the general public are reluctant to donate DNA for research, the choices patients actually make about sharing their clinical genomic data for future re-use (research or clinical) are unknown. We ascertained the data-sharing choices of 1515 patients having genomic testing for inherited conditions or cancer treatment from clinical consent forms. "

Genomic analysis of 116 autism families strengthens known risk genes and highlights promising candidates
M Viggiano et al, NPJ Genomic Medicine, March 22, 2024 (Posted: Mar 23, 2024 6AM)

From the abstract: "Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component in which rare variants contribute significantly to risk. We performed whole genome and/or exome sequencing (WGS and WES) and SNP-array analysis to identify both rare sequence and copy number variants (SNVs and CNVs) in 435 individuals from 116 ASD families. We identified 37 rare potentially damaging de novo SNVs (pdSNVs) in the cases (n?=?144). "

Genomes in clinical care
O Riess et al, NPJ Genomic Medicine, March 14, 2024 (Posted: Mar 18, 2024 9AM)

From the abstract: "In the era of precision medicine, genome sequencing (GS) has become more affordable and the importance of genomics and multi-omics in clinical care is increasingly being recognized. However, how to scale and effectively implement GS on an institutional level remains a challenge for many. Here, we present Genome First and Ge-Med, two clinical implementation studies focused on identifying the key pillars and processes that are required to make routine GS and predictive genomics a reality in the clinical setting. "

The interplay of ethics and genetic technologies in balancing the social valuation of the human genome in UNESCO declarations
H Gaydarska et al, EJHG, February 15, 2024 (Posted: Feb 15, 2024 9AM)

From the abstract: " This study investigates changes in the social valuation of the human genome over the more than 30 years since the establishment of the Human Genome Project. It offers a descriptive sociological analysis of the three waves of this valuation, mainly by considering three key UNESCO declarations and a relevant report. These waves represent a shifting balance between collectivism and individualism."

Genetics Adviser: The development and usability testing of a new patient digital health application to support clinical genomic testing.
M CLausen et al, Genetics in Med Open, January 24, 2024 (Posted: Jan 23, 2024 8AM)

From the abstract: " Increasing demand for genomic testing coupled with genetics workforce shortages has placed unsustainable pressure on standard models of care. Digital tools can offer improved access, efficiency, and cost savings. We created a patient-facing digital health application to support genomic testing. We developed the digital application through user-centered design, guided by an advisory board. We tested its usability and acceptability with patients, practitioners and members of the general public using mixed methods."

Diagnostic delay in monogenic disease: a scoping review
RJ Tinker et al, Genetics in Medicine, January 18, 2024 (Posted: Jan 18, 2024 2PM)

From the abstract: "Diagnostic delay in monogenic disease is reportedly common. We conducted a scoping review investigating variability in study design, results, and conclusions. Our search identified 259 articles quantifying diagnostic delay in 111 distinct monogenetic diseases. Median reported diagnostic delay for all studies collectively in monogenetic diseases was 5.0 years (IQR 2- 10). There was major variation in the reported delay within individual monogenetic diseases. Shorter delay was associated with disorders of childhood metabolism, immunity, and development. "

Reanalysis of genomic data, how do we do it now and what if we automate it? A qualitative study
Z Fehlberg et al, EJHG, January 12, 2023 (Posted: Jan 12, 2024 7AM)

From the abstract: " Automating reanalysis of genomic data for undiagnosed rare disease patients presents a paradigm shift in how clinical genomics is delivered. We aimed to map the current manual and proposed automated approach to reanalysis and identify possible implementation strategies to address clinical and laboratory staff’s perceived challenges to automation. "

Characterizing the pathogenicity of genetic variants: the consequences of context.
Timothy H Ciesielski et al. NPJ Genom Med 2024 1 (1) 3 (Posted: Jan 11, 2024 7AM)

From the abstract: "Beyond initial discovery of a pathogenic variant, establishing that a variant is recurrently associated with disease is important for understanding clinical impact and disease etiology. Disappointingly, our ability to characterize pathogenicity under varied circumstances is limited. Here we discuss the role of genetic and environmental background and how it affects variant penetrance and outcomes. Specifically, genetic and environmental settings determine penetrance, and we should expect lower penetrance where contexts are diverse. "

Genetic ancestry and diagnostic yield of exome sequencing in a diverse population
Y Mavura et al, NPJ Genomic Medicine, January 3, 2024 (Posted: Jan 03, 2024 8AM)

From the abstract: "It has been suggested that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations. "

Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications
A Duffy et al, Nature Genetics, January 2, 2024 (Posted: Jan 03, 2024 8AM)

From the abstract: "Studies have shown that drug targets with human genetic support are more likely to succeed in clinical trials. Hence, a tool integrating genetic evidence to prioritize drug target genes is beneficial for drug discovery. We built a genetic priority score (GPS) by integrating eight genetic features with drug indications from the Open Targets and SIDER databases. The top 0.83%, 0.28% and 0.19% of the GPS conferred a 5.3-, 9.9- and 11.0-fold increased effect of having an indication, respectively. "

Genomic medicine year in review: 2023.
Teri A Manolio et al. Am J Hum Genet 2023 12 (12) 1992-1995 (Posted: Dec 14, 2023 8AM)

From the article: "Highlighted papers in genomic medicine implementation research in 2023 continued several themes from earlier years, particularly in diagnostic testing of critically ill infants, genetic diagnosis of rare syndromes, and prenatal and population-based screening for monogenic syndromes. Pharmacogenomics was also highlighted with the first large-scale, multi-country clinical trial of multiple gene-drug pairs. The success of the first CRISPR-Cas9-based therapeutic trial in sickle cell disease and the independence of polygenic risk scores and family history in complex disease risk assessment were also highlighted, as were the high rate of insurance denials for exome sequencing that frequently turned out to be diagnostic. "

Will variants of uncertain significance still exist in 2030?
Douglas M Fowler et al. Am J Hum Genet 2023 12 (Posted: Dec 13, 2023 7AM)

From the abstract: "In 2020, the National Human Genome Research Institute (NHGRI) made ten “bold predictions,” including that “the clinical relevance of all encountered genomic variants will be readily predictable, rendering the diagnostic designation ‘variant of uncertain significance (VUS)’ obsolete.” We discuss the prospects for this prediction, arguing that many, if not most, VUS in coding regions will be resolved by 2030. We outline a confluence of recent changes making this possible. "

Envisioning a new era: Complete genetic information from routine, telomere-to-telomere genomes
KH Miga et al, AJHG, November 2023 (Posted: Nov 20, 2023 8AM)

From the abstract: "With declining costs and increasing democratization of technology, we suggest that complete genome assemblies, where both parental haplotypes are phased telomere to telomere, will become standard in human genetics. Soon, even in clinical settings where rigorous sample-handling standards must be met, affected individuals could have reference-grade genomes fully sequenced and assembled in just a few hours given advances in technology, computational processing, and annotation. "

Population-based prevalence and mutational landscape of von Willebrand disease using large-scale genetic databases
O Seidizadeh et al, NPJ Genomic Medicine, October 16, 2023 (Posted: Oct 17, 2023 10AM)

From the abstract: "The global prevalence of dominant VWD in 1000 individuals was established to be 74 for type 1, 3 for 2A, 3 for 2B and 6 for 2M. The global prevalences for recessive VWD forms (type 2N and type 3) were 0.31 and 0.7 in 1000 individuals, respectively. This comprehensive analysis provided a global mutational landscape of VWF by means of 927 already reported variants in the HGMD and LOVD datasets and 287 novel pathogenic variants identified in the gnomAD. Our results reveal that there is a considerably higher than expected prevalence of putative disease alleles and variants associated with VWD and suggest that a large number of VWD patients are undiagnosed. "

The burden of splice-disrupting variants in inherited heart disease and unexplained sudden cardiac death
ES Singer et al, NPJ Genomic Medicine, October 11, 2023 (Posted: Oct 11, 2023 4PM)

From the abstract: "We performed burden testing of rare splice-disrupting variants in people with inherited heart disease and sudden unexplained death compared to 125,748 population controls. ClinGen definitively disease-associated inherited heart disease genes were amplified using RNA extracted from fresh blood, derived cardiomyocytes, and myectomy tissue. Variants were functionally assessed and classified for pathogenicity. We found 88 in silico-predicted splice-disrupting variants in 128 out of 1242 (10.3%) unrelated participants. "

Ethics of artificial intelligence in prenatal and pediatric genomic medicine.
Simon Coghlan et al. J Community Genet 2023 10 (Posted: Oct 07, 2023 8AM)

From the abstract: " This paper examines the ethics of introducing emerging forms of artificial intelligence (AI) into prenatal and pediatric genomic medicine. Application of genomic AI to these early life settings has not received much attention in the ethics literature. We focus on three contexts: (1) prenatal genomic sequencing for possible fetal abnormalities, (2) rapid genomic sequencing for critically ill children, and (3) reanalysis of genomic data obtained from children for diagnostic purposes."

From target discovery to clinical drug development with human genetics.
Katerina Trajanoska et al. Nature 2023 8 (7975) 737-745 (Posted: Aug 28, 2023 9AM)

From the abstract: "We identified 40 germline genetic observations that led directly to new targets and subsequently to novel approved therapies for 36 rare and 4 common conditions. The median time between genetic target discovery and drug approval was 25 years. Most of the genetically driven therapies for rare diseases compensate for disease-causing loss-of-function mutations. The therapies approved for common conditions are all inhibitors designed to pharmacologically mimic the natural, disease-protective effects of rare loss-of-function variants."

Your cells don’t have the genome you were born with. Project aims to chart impact of new mutations
M Leslie, Science, August 15, 2023 (Posted: Aug 21, 2023 8AM)

Every person is actually a mosaic of genomes, varying across the body and often within the same organ or tissue. These DNA changes introduce a diversity to the body’s somatic, or nonreproductive, cells that may be as important to health as the more pervasive alterations inherited from parents. Now, the National Institutes of Health (NIH) has launched a 5-year million project to map this universe of genomic diversity—and probe why it matters.

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 Brand (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.

Rapid Genome Sequencing for Diagnosing Critically Ill Infants and Children: From Evidence to Equitable Implementation
CDC webinar, November 30, 2023 (Posted: Jul 21, 2023 9AM)

Dr. Stephen F. Kingsmore is president/CEO of Rady Children’s Institute for Genomic Medicine (RCIGM), where he leads a multidisciplinary team that is pioneering the use of rapid genome sequencing to diagnose critically ill children, implement precision medicine, and screen for approximately 500 genetic disorders. Dr. Kingsmore holds two Guinness World Records for achieving the fastest molecular diagnosis using whole genome sequencing.

ClinVar and HGMD genomic variant classification accuracy has improved over time, as measured by implied disease burden.
Andrew G Sharo et al. Genome Med 2023 7 (1) 51 (Posted: Jul 19, 2023 7AM)

Curated databases of genetic variants assist clinicians and researchers in interpreting genetic variation. Yet, these databases contain some misclassified variants. It is unclear whether variant misclassification is abating as these databases rapidly grow and implement new guidelines. We found that variant classification guidelines and allele frequency databases comprising genetically diverse samples are important factors in reclassification. We also discovered that ClinVar variants common in European and South Asian individuals were more likely to be reclassified to a lower confidence category,

Provision and Availability of Genomic Medicine Services in Level IV Neonatal Intensive Care Units
MH Wojcik et al, Genet Med, July 6, 2023 (Posted: Jul 07, 2023 9AM)

We developed and distributed a novel survey to the 43 level IV NICUs belonging to the Children's Hospitals Neonatal Consortium (CHNC), requesting a single response per site from a clinician with knowledge of the provision of genomic medicine services. Overall response rate was 74% (32/43). While chromosomal microarray and exome or genome sequencing (ES or GS) were universally available, access was restricted for 22% (7/32) and 81% (26/32) of centers, respectively. The most common restriction on ES or GS was requiring approval by a specialist (41%, 13/32). Rapid ES/GS was available in 69% of NICUs (22/32). Availability of same-day genetics consultative services was limited (41%, 13/32 sites),

The Gregor Mendel Bicentennial Tribute-Enduring Mementos of the Founder of Genetics.
John J Mulvihill et al. JAMA 2023 6 (Posted: Jul 01, 2023 9AM)

A More Diverse and Complete Reference Human Genome Is Poised to Change Medicine.
Jyoti Madhusoodanan et al. JAMA 2023 6 (Posted: Jul 01, 2023 9AM)

It’s been more than 20 years since the initial draft of the human genome—a single, incomplete sequence based largely on one person’s DNA—was unveiled. Last month, scientists published the first draft of a human “pangenome” in Nature, a collection of 94 nearly complete, high-quality DNA sequences, representing both sets of chromosomes from 47 individuals with diverse ancestral backgrounds.

Tracking genetic variants in the biomedical literature using LitVar 2.0.
Alexis Allot et al. Nat Genet 2023 6 (6) 901-903 (Posted: Jun 22, 2023 7AM)

Keeping up with the latest variant-related research is vital for genomic medicine. Here we present LitVar 2.0, a significantly improved web-based system to accurately search for genetic variants in the unstructured literature. LitVar 2.0 provides a unified search of full text and supplementary data, and improved variant recognition accuracy.

Studying the impact of translational genomic research: Lessons from eMERGE
E Clayton et al, AJHG, June 21, 2023 (Posted: Jun 21, 2023 7AM)

We divide the domains in which we experienced challenges into four broad categories: (1) study design, including recruitment of more diverse groups; (2) consent; (3) returning results to participants and their health care providers (HCPs); and (4) assessment of follow-up care of participants and measuring the impact of research on participants and their families,

siRNAs-A New Class of Medicines.
Anastasia Khvorova et al. JAMA 2023 6 (Posted: Jun 13, 2023 8AM)

Programmable siRNA therapeutics have demonstrated effectiveness for treating an increasing number of rare conditions. siRNAs promise to expand the therapeutic toolbox of clinicians. There are currently 5 approved siRNA drugs including inclisiran for hypercholesterolemia, givosiran for acute hepatic porphyria, lumasiran for primary hyperoxaluria type, as well aspatisiran and vutrisiran for hereditary transthyretin-mediated amyloidosis in adults, with other drugs in clinical development.

Diagnostic yield of pediatric and prenatal exome sequencing in a diverse population
A Slavotinek et al, NPJ Genomic Medicine, May 26, 2023 (Posted: May 27, 2023 7AM)

We identified definitive positive or probable positive results in 201/845 (23.8%) patients, with a significantly higher diagnostic rate in pediatric (26.7%) compared to prenatal patients (19.0%) (P?=?0.01). For both pediatric and prenatal patients, the diagnostic yield and frequency of inconclusive findings did not differ significantly between URM and non-URM patients or between patients with US status and those without US status.

A Pooled Electronic Consultation Program to Improve Access to Genetics Specialists.
Emma K Folkerts et al. medRxiv 2023 2 (Posted: May 24, 2023 9AM)

An e-Consult service was created to address genomics-related questions at the point of care. In its first year, the e-Consult service triaged 153 requests and completed 122 in median of 2.0 days. Of the 97 e-Consults with actionable recommendations, there was documentation that most ordering clinicians followed through (82%). A variety of providers used the service, although the majority (77%) were generalists. e-Consult models should be considered as one way to increase access to genetics expertise.

First human 'pangenome' aims to catalogue genetic diversity.
Layal Liverpool et al. Nature 2023 5 (Posted: May 12, 2023 6AM)

More than 20 years after the first draft genome from the landmark Human Genome Project was released, researchers have published a draft human ‘pangenome’ — a snapshot of what is poised to become a new reference for genetic research that captures more of human diversity than has been previously available. Geneticists have welcomed the milestone, while also highlighting key ethical considerations surrounding the effort to make genome research more inclusive.

‘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.

Genomics in Clinical Practice
JE Posey et al, NEJM, April 12, 2023 (Posted: Apr 13, 2023 6AM)

The field of clinical genomics has been particularly challenged by the continuous evolution of both knowledge (e.g., the steady pace of new disease gene discoveries) and molecular diagnostic techniques. “Best practices” have often been more readily defined according to the requirements of health care systems and payers rather than the findings from any true, broad assessment of diagnostic utility.

Realizing the Potential of Genomics across the Continuum of Precision Health Care: Proceedings of a Workshop (2023)
NASEM, March 30, 2023 (Posted: Mar 30, 2023 10AM)

The National Academies Roundtable on Genomics and Precision Health hosted a public workshop that examined how genomic data are used in health care, outside of the traditional settings for clinical genetics. The workshop identified opportunities for advancement of precision health care delivery. The event also explored how patients, clinicians, and payers assess and act upon the risks and benefits of genomic screening and diagnostic testing. Discussions focused on strategies to ensure that genomic applications are responsibly and equitably adopted to benefit populations as well as individuals over time.

Medical Genetics Awareness Week,
ACMG, March 2023 (Posted: Mar 11, 2023 2PM)

The goal of Medical Genetics Awareness Week is to raise awareness of the invaluable contributions that medical genetics healthcare professionals make in the diagnosis, management and prevention of genetic diseases, and the difference these professionals make in the lives of patients and families. The theme of Medical Genetics Awareness Week is “Celebrating the Contributions of the Entire Medical Genetics Team to Patient Care and Public Health.”

Host genomics for better infectious disease treatment
H Carr, PHG Foundation, March 6, 2023 (Posted: Mar 10, 2023 3PM)

Individuals can respond very differently to the same infectious disease, even when they have similar characteristics, comorbidities, and environmental exposures. Host genomics is the field that looks for genetic differences that help to explain the variations in response at certain points of an infection. While the COVID-19 pandemic significantly raised the profile of host genomics as a tool to better understand severe COVID-19, before the pandemic, scientists had been exploring host genomics to understand differences in host response to various infectious diseases.

Australian Genomics: Outcomes of a 5-year national program to accelerate the integration of genomics in healthcare
Z Stark et al, Cell Press, March 2, 2023 (Posted: Mar 03, 2023 8AM)

Australian Genomics is a national collaborative partnership of more than 100 organizations piloting a whole-of-system approach to integrating genomics into healthcare, based on federation principles. In the first five years of operation, Australian Genomics has evaluated the outcomes of genomic testing in more than 5,200 individuals across 19 rare disease and cancer flagship studies.

The Promise and Challenges of Implementing Pharmacogenomics to Improve Population Health: Where Are we Heading with Preemptive Pharmacogenomic Screening?
CDC Webinar, September 14, 2023 Brand (Posted: Feb 24, 2023 8AM)

With genotyping technologies now widely available and decreasing in cost, implementing pharmacogenomics into clinical practice is widely viewed as an initial step in mainstreaming genomic medicine. The benefits of pharmacogenomic testing before starting drug therapy has been well documented for several single gene-drug combinations. In addition, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel is being rigorously assessed. However, major challenges of implementation lie at the point of integration into healthcare systems, including the modification of clinical pathways and a large knowledge gap in pharmacogenomics in the healthcare workforce.

Mendelian inheritance revisited: dominance and recessiveness in medical genetics
J Zschocke et al, Nat Rev Genetics, February 20, 2023 (Posted: Feb 20, 2023 8AM)

Understanding the consequences of genotype for phenotype (which ranges from molecule-level effects to whole-organism traits) is at the core of genetic diagnostics in medicine. Many measures of the deleteriousness of individual alleles exist, but these have limitations for predicting the clinical consequences. Various mechanisms can protect the organism from the adverse effects of functional variants, especially when the variant is paired with a wild type allele.

Scalable, high quality, whole genome sequencing from archived, newborn, dried blood spots
Y Ding et al, NPJ Genomic Medicine, February 14, 2023 (Posted: Feb 14, 2023 7AM)

We describe simple methods for gDNA extraction and WGS library preparation from several types of DBS. We tested these methods in DBS from 25 individuals who had previously undergone diagnostic, clinical WGS and 29 randomly selected DBS cards collected for NBS from the California State Biobank. While gDNA from DBS had significantly less yield than from EDTA blood from the same individuals, it was of sufficient quality and quantity for WGS without PCR.

How rare mutations contribute to complex traits
LM Evans et al, Nature, February 8, 2023 (Posted: Feb 09, 2023 6AM)

Our understanding of the genetic mutations that affect complex human traits — such as height, smoking-related behaviour or the risk of diabetes — has been vastly broadened by genome-wide association studies (GWASs). But such research has focused largely on associations between traits of interest and variants that are common in the human population. Rare variants pose challenges to GWASs, because they can be studied using only large samples and in-depth genetic information, and can be more strongly confounded by non-genetic factors than can common variants,

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.

Advancing Genomic Medicine in Africa: Work in Progress
J Osei et al, CDC Blog Post, January 9, 2023 Brand (Posted: Jan 11, 2023 6AM)

Continued progress in genomic medicine to improve public health in Africa will require local-level capacity, expertise, and partnerships to conduct research and to assure the safe and equitable implementation of the field’s initiatives. Broad support from all interested parties including national and international governing authorities is crucial to guarantee the long-term sustainability of GM initiatives on the continent.

Returning integrated genomic risk and clinical recommendations: the eMERGE study
JE Linder et al, Genetics in Medicine, January 8, 2023 (Posted: Jan 09, 2023 6AM)

To enable integrated genetic risk assessment, the eMERGE (electronic MEdical Records and GEnomics) network is enrolling 25,000 diverse individuals in a prospective cohort study across 10 sites. The network developed methods to return cross-ancestry polygenic risk scores (PRS), monogenic risks, family history, and clinical risk assessments via a Genome Informed Risk Assessment (GIRA) report

RNA Sequencing as a Diagnostic Tool.
Ketkar Shamika et al. JAMA 2022 12 (Posted: Dec 20, 2022 8AM)

RNA sequencing (RNA-seq) is a new tool in the genetic diagnostic laboratory made possible by the advent of low-cost, high-throughput, next-generation sequencing technology. Historically, RNA studies were limited to gene expression using microarray technology for the detection of gene rearrangements and quantification of gene expression for predefined genes. RNA-seq allows detection of qualitative and quantitative changes in RNA expression across the genome in clinical samples and is increasingly being used as an adjunct to diagnostic exome sequencing and whole-genome sequencing.

Genetic futurism.
et al. Nature genetics 2022 12 (12) 1757 (Posted: Dec 16, 2022 8AM)

Large-scale genotyping and phenotyping efforts, including biobanks, have revolutionized our understanding of the genetic architecture of human traits and diseases. Years of ever-larger genome-wide association studies (GWAS) have produced a catalog of genetic variants that contribute to complex traits. A corollary of this research has been the development of personalized polygenic scores (PGS) or polygenic risk scores (PRS).

The implementation of large-scale genomic screening or diagnostic programmes: A rapid evidence review
GAA Garavito et al, EJHG, December 14, 2022 (Posted: Dec 14, 2022 5PM)

The review included thirty articles drawing on sixteen countries. A wide range of factors was cited as critical to the successful implementation of genomics programmes. These included having policy frameworks, regulations, guidelines; clinical decision support tools; access to genetic counselling; and education and training for healthcare staff. The high costs of implementing and integrating genomics into healthcare were also often barriers to stakeholders. National genomics programmes are complex and require the generation of evidence and addressing implementation challenges.

Genomic Medicine Year in Review: 2022.
Manolio Teri A et al. American journal of human genetics 2022 12 (12) 2101-2104 (Posted: Dec 11, 2022 6AM)

Ten selected papers in genomic medicine implementation research in 2022 highlight the feasibility and practical value of various genomic screening methods, pharmacogenomic-guided treatment, and genomic-based rare disease diagnoses. Notably, genomic medicine resources showed the most substantial growth of any category reflecting in part the growing number of rigorous clinical and implementation studies that provide evidence and guidance for, and promote interest in, the clinical implementation of genomic medicine.

Managing expectations, rights, and duties in large-scale genomics initiatives: a European comparison.
Horn Ruth et al. European journal of human genetics : EJHG 2022 12 (Posted: Dec 07, 2022 8AM)

This article reports on the findings of an international workshop in 2021. We focus specifically on how collection, storage and sharing of genomic data may pose challenges to established principles and values such as trust, confidentiality, and privacy in countries that have implemented, or are about to implement, large-scale national genomic initiatives. These challenges impact the relationships between patients/citizens and medicine/science, and on each party’s rights and duties towards each other.

Integrating genomics into the care of people with palliative needs: A global scoping review of policy recommendations.
White Stephanie et al. Public health genomics 2022 11 (Posted: Nov 20, 2022 7AM)

To identify policy recommendations related to: (1) integrating genomics into the care of patients with palliative care needs and their families, and (2) care of the family unit, we performed a scoping review of palliative care and genomic policies. Two of 78 policies recommended integrating genomics into palliative care. Six palliative care policies mentioned genomics in background information but were without relevant recommendations. No genomics policies mentioned palliative care in the background information.

Medicine and health of 21st Century: Not just a high biotech-driven solution.
Assidi Mourad et al. NPJ genomic medicine 2022 11 (1) 67 (Posted: Nov 16, 2022 8AM)

Although the potential of biotechnology is motivating, we should not lose sight of approaches that may not seem as glamorous but can have large impacts on the healthcare of many and across disparate population groups. A balanced approach of “omics and big data” solution in contemporary health systems along with a large scale, simpler, and suitable strategies should be defined with expectations properly managed.

The landscape of mRNA nanomedicine
X Huang et al, Nature Medicine, November 10, 2022 (Posted: Nov 11, 2022 7AM)

Messenger RNA (mRNA) is an emerging class of therapeutic agent for the prevention and treatment of a wide range of diseases. The recent success of the two highly efficacious mRNA vaccines to protect against COVID-19 highlights the huge potential of mRNA technology for revolutionizing life science and medical research. Challenges related to mRNA stability and immunogenicity, as well as in vivo delivery and the ability to cross multiple biological barriers, have been largely addressed. In this Review, we present the latest advances and innovations in the growing field of mRNA nanomedicine, in the context of ongoing clinical translation and future directions to improve clinical efficacy.

Making the most of genomics: supporting clinical research and care
P Brice, PHG Foundation, November 10, 2022 (Posted: Nov 10, 2022 7AM)

It will not be possible to realise the full potential of genomics for health, even in a country that is currently an acknowledged global leader in genomic medicine and research, without fundamental changes to connect data, research and practice. Therefore, calls for speedy, collaborative, cross-sector working (including patients and citizens) to design robust, resilient approaches that offer health and economic benefits for everyone should continue to be recognised,

Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing.
Macken William L et al. Nature communications 2022 11 (1) 6324 (Posted: Nov 08, 2022 7AM)

Here, we show that specialist multidisciplinary analysis of WGS, following an initial ‘no primary findings’ (NPF) report, improves diagnostic rates and alters management. We undertook WGS in 102 adults with diagnostically challenging primary mitochondrial disease phenotypes. NPF cases were reviewed by a genomic medicine team, thus enabling bespoke informatic approaches, co-ordinated phenotypic validation, and functional work. We enhanced the diagnostic rate from 16.7% to 31.4%, with management implications for all new diagnoses.

The genetic counsellor role in the United Kingdom
A Middleton et al, EJHG, November 1, 2022 (Posted: Nov 01, 2022 11AM)

Genetic counsellors are an internationally recognized group of highly skilled healthcare professionals with training and expertise in genomic medicine and counselling skills. The delivery of genetic counselling in a clinical setting is underpinned by evidence, genetic counselling theory, uses established, validated outcome measures to evaluate success and is highly valued by patients. The number of genetic counsellors globally is approximately 7000, practicing in at least 28 countries. In the UK, there are approximately 300 genetic counsellors, the vast majority practicing clinically in the publicly funded National Health Service.

Scope of professional roles for genetic counsellors and clinical geneticists in the United Kingdom
A Middleton et al, EJHG, November 1, 2022 (Posted: Nov 01, 2022 11AM)

Accelerating genomic medicine in the NHS
NHS England, October 2022 (Posted: Oct 30, 2022 0PM)

As we bring the benefits of genomics to patients and our population, we need a comprehensive and ambitious national approach covering prevention, diagnosis and targeted treatments that enables patients, families and carers to participate in shared decision making. This strategy sets out four priority areas to this approach: 1. Embedding genomics across the NHS, through a world leading innovative service model from primary and community care through to specialist and tertiary care. 2. Delivering equitable genomic testing for improved outcomes in cancer, rare, inherited and common diseases and in enabling precision medicine and reducing adverse drug reactions. 3. Enabling genomics to be at the forefront of the data and digital revolution, ensuring genomic data can be interpreted and informed by other diagnostic and clinical data. 4. Evolving the service through cutting-edge science, research and innovation to ensure that patients can benefit from rapid implementation of advances.

The NHS’s new strategy for genomics: Five key takeaways
UK Genomics Education Program, October 25, 2022 (Posted: Oct 30, 2022 0PM)

We look at the new ‘Accelerating genomic medicine in the NHS’ report, an ambitious first in genomics strategy for the health service, and what it means for healthcare professionals. Here are five things we learned from the report: 1. WES out, WGS in, for children in intensive care. 2. Pharmacogenomics’ growing role. 3. Creating a new digital infrastructure. 4. Representing the patient voice. 5. Genomics upskilling for all.

Genetics professionals are key to the integration of genetic testing within the practice of frontline clinicians.
Scheuner Maren T et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 10 (Posted: Oct 30, 2022 10AM)

We administered a web-based survey to clinicians at 20 VA facilities. Physicians, nurse practitioners, physician assistants, and pharmacists were eligible. We excluded genetics providers and clinicians not seeing patients. We used multiple logistic regression to evaluate the associations between clinician characteristics and experience with genetics. Only 20.8% of the respondents reported feeling prepared to use genetic tests and 13.0% of the respondents were currently ordering genetic tests; although, it was usually only 1 or 2 a year. Delivery of genetic tests without involving genetics providers was preferred by only 7.9% of the respondents.

Co-design, implementation, and evaluation of plain language genomic test reports
GR Brett et al, NPJ Genomic Medicine, October 22, 2022 (Posted: Oct 22, 2022 0PM)

Through co-design involving patient groups, plain language experts, educators, and genetic health professionals, plain language genomic test report templates were produced for common test outcomes in rare diseases. Eight plain language genomic test report templates were developed. These reports were piloted and evaluated as part of a national pediatric ultra-rapid genomic testing program. Family and genetic health professional experiences with report layout, content, and use were explored using surveys.

Resource allocation in genetic and genomic medicine
J Buchanan et al, J Community Genetics, September 24, 2022 (Posted: Sep 26, 2022 7AM)

Integrating genomic medicine within national health services has so far not been straightforward . Amongst other considerations, effective translation requires that careful attention is paid to issues surrounding priority setting and resource allocation. Commissioning genomic medicine services in a fair, equitable, and appropriate manner necessitates rigorous exploration of the ethical, policy, and practical implications, including factors such as cost, opportunity cost, clinical effectiveness, cost-effectiveness, need, ability to benefit, and procedural fairness.

Trends in Tier 1 Genomic Applications 2013-2022
M Clyne et al, CDC Blog Post, September 20, 2022 Brand (Posted: Sep 20, 2022 2PM)

The CDC Tier 1 genomic applications database can help consumers, providers, health care organizations and public health programs accelerate the translation of genomic discoveries into improved population health. Advances in genomics and precision medicine are proceeding at a rapid pace. Many genomic tests have reached clinical practice without clear indication as to whether their use will actually improve health. In order to provide general information to healthcare providers and the general public, in 2014 our office introduced a simple approach for classifying genomic applications based upon 1) type of evidence and 2) recommendation for use of genomic applications. This systematic classification approach assigns genomic applications into one of three tiers.

Understanding the Patient Experience of Receiving Clinically Actionable Genetic Results from the MyCode Community Health Initiative, a Population-Based Genomic Screening Initiative
A Baker et al, J Per Medicine, September 15, 2022 (Posted: Sep 15, 2022 7AM)

Coding of 63 interviews among 60 participants revealed that participants were satisfied with the results disclosure process, initially experienced a range of positive, neutral, and negative psychological reactions to results, adjusted positively to results over time, undertook clinically indicated actions in response to results, and communicated results with relatives to whom they felt emotionally close.

Human genomics vs Clinical genomics
E Topol, Ground Truths, September 11, 2022 (Posted: Sep 12, 2022 1PM)

For decades, the genomics research community has been in high gear productivity, extensively publishing data about medical conditions. But so little has reached clinical practice outside of a few exceptions like rapid neonatal sequencing or adults with serious, undiagnosed conditions, or in specific use cases in cancer. Even those are only performed by a limited number of health systems.

A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility
G Voloudakis et al, NPJ Genomic Medicine, September 5, 2022 (Posted: Sep 05, 2022 6AM)

Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility. In a series of validation steps, we show that predicted GReX upregulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways.

Integrating rapid exome sequencing into NICU clinical care after a pilot research study
AM D'Gama et al, NPJ Genomic Medicine, September 5, 2022 (Posted: Sep 05, 2022 6AM)

Compared to other genetic tests, rapid ES had similar or higher diagnostic yield and similar or decreased time to result. Overall, rapid ES was utilized in the NICU after the pilot research study, often as the first-tier sequencing test, and could identify the majority of disease-causing variants, shorten the diagnostic odyssey, and impact clinical care. Based on our experience, we have identified strategies to optimize the clinical implementation of rapid ES in the NICU.

Guidelines, guidelines everywhere—and still I’m not sure what to do
A McNeill, AJHG, August 29, 2022 (Posted: Aug 29, 2022 9AM)

Mutational and splicing landscape in a cohort of 43,000 patients tested for hereditary cancer
C Horton et al, NPJ Genomic Medicine, August 25, 2022 (Posted: Aug 26, 2022 8AM)

DNA germline genetic testing can identify individuals with cancer susceptibility. However, DNA sequencing alone is limited in its detection and classification of mRNA splicing variants, particularly those located far from coding sequences. Here we address the limitations of splicing variant identification and interpretation by pairing DNA and RNA sequencing and describe the mutational and splicing landscape in a clinical cohort of 43,524 individuals undergoing genetic testing for hereditary cancer.

Methylation risk scores are associated with a collection of phenotypes within electronic health record systems
M Thompson et al, NPJ Genomic Medicine, August 26, 2022 (Posted: Aug 26, 2022 8AM)

We considered the epigenetic analog of PRS, methylation risk scores (MRS), a linear combination of methylation states. We measured methylation across a large cohort (n?=?831) of diverse samples in the UCLA Health biobank, for which both genetic and complete EHR data are available. We constructed MRS for 607 phenotypes spanning diagnoses, clinical lab tests, and medication prescriptions. When added to a baseline set of predictive features, MRS significantly improved the imputation of 139 outcomes, whereas the PRS improved only 22 (median improvement for methylation 10.74%, 141.52%, and 15.46% in medications, labs, and diagnosis codes, respectively, whereas genotypes only improved the labs at a median increase of 18.42%).

Discovering monogenic patients with a confirmed molecular diagnosis in millions of clinical notes with MonoMiner.
Wu David Wei et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 8 (Posted: Aug 18, 2022 1PM)

We define a subset (4461) of OMIM diseases that have at least 1 known monogenic causal gene. We then introduce MonoMiner, a natural language processing framework to identify molecularly confirmed monogenic patients from free-text clinical notes. We show that ICD-10-CM codes cover only a fraction of monogenic diseases and that even where available, ICD-10-CM code?based patient retrieval offers 0.14 precision. Searching by causal gene symbol offers great recall but has an even worse 0.07 precision. MonoMiner achieves 6 to 11 times higher precision (0.80), with 0.87 precision on disease diagnosis alone, tagging 4259 patients with 560 monogenic diseases and 534 causal genes, at 0.48 recall.

Genomic Medicine's Critical Outcome Measure-Utility.
Smith Hadley Stevens et al. JAMA network open 2022 8 (8) e2225988 (Posted: Aug 15, 2022 7PM)

In more than a decade since genomic sequencing was first used for a patient diagnosis, clinical applications of this technology have rapidly increased. Successful early applications resulting in patient diagnoses and changes in care trajectories were primarily communicated through case reports.2 Larger numbers of patients now have genetic sequencing performed as part of research cohorts and clinical care, allowing calculations of the average effect of the intervention; however, the influence of compelling individual patient stories on outcomes reporting remains.

Measures of Utility Among Studies of Genomic Medicine for Critically Ill Infants: A Systematic Review.
Callahan Katharine Press et al. JAMA network open 2022 8 (8) e2225980 (Posted: Aug 15, 2022 7PM)

In this systematic review of 21 studies including 1654 infants, utility was heterogeneously measured and reported but generally fit into 5 categories: treatment change, redirection of care, prognostic information, reproductive information, and screening or subspecialty referral. Measurement of utility was inconsistent, focused on documenting change rather than assessing meaningful benefit, and omitted patient-reported benefits, utility of negative or uncertain results, and disutility (harms).

Use of eConsult to enhance genetics service delivery in primary care: A multimethod study.
Carroll June C et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 8 (Posted: Aug 11, 2022 11AM)

Electronic consultation (eConsult) is a freely-available secure online platform connecting primary care providers (PCPs) to geneticists. Our purpose was to determine whether eConsult is effective in improving genetics service delivery in primary care. eConsult offers a potential solution for receiving timely genetics advice and avoiding unnecessary patient referrals, however, greater effect on access and wait times will need systematic integration into PCP and geneticist practice.

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders.
Boonsawat Paranchai et al. NPJ genomic medicine 2022 7 (1) 45 (Posted: Jul 31, 2022 7AM)

Supporting undiagnosed participants when clinical genomics studies end.
Halley Meghan C et al. Nature genetics 2022 7 (Posted: Jul 29, 2022 8AM)

Many large research initiatives have cumulatively enrolled thousands of patients with a range of complex medical issues but no clear genetic etiology. However, it is unclear how researchers, institutions and funders should manage the data and relationships with those participants who remain undiagnosed when these studies end. In this Comment, we outline the current literature relevant to post-study obligations in clinical genomics research and discuss the application of current guidelines to research with undiagnosed participants.

The deceptive simplicity of mendelian genetics.
McLysaght Aoife et al. PLoS biology 2022 7 (7) e3001691 (Posted: Jul 23, 2022 8AM)

Mendel, a genius experimentalist, meticulously uncovered the genetic basis of heredity in work that transformed the science of biology. But does the alluring simplicity of Mendel’s laws sometimes obscure the true complexity of genetics? We are not mere vessels for our genes. Humans, uniquely, and starting with Mendel, are the only species that has developed an understanding of heredity and how genetic information is transmitted across generations and how genes help shape all biological life on this planet. Though we describe supposed single-gene deterministic traits as “mendelian,” I know of no evidence that suggests Mendel himself conceived of such a fanciful system.

Accelerating access to genomics for global health: promotion, implementation, collaboration, and ethical, legal, and social issues: a report of the WHO Science Council
WHO, July 2022 (Posted: Jul 19, 2022 9AM)

This publication presents the recommendations of the WHO Science Council to the Director-General on accelerating access to genomics for global health. A series of workshops was held in 2021 to gather information and perspectives on this topic. Fifteen actions are recommended to achieve the goal of accelerating access to genomics for global health.

How did Mendel arrive at his discoveries?
van Dijk Peter J et al. Nature genetics 2022 7 (7) 926-933 (Posted: Jul 19, 2022 7AM)

Find a Genetic Clinic
ACMG, 2022 (Posted: Jul 10, 2022 7AM)

ACMG's "Find a Genetics Clinic" allow individuals to search for genetics clinics across the United States. The directory contains the locations of genetics clinics that have requested to be listed. Select one or more Specialty Area(s) Adult Genetics Cancer Genetics (includes cancer risk assessment, screening or prevention; hereditary/familial cancer) Cardiovascular Genetics General Genetics (includes Medical Genetics and Birth Defects) Genetic Counseling Metabolic Neurogenetics Pediatric Genetics Prenatal Genetics (includes prenatal diagnosis, antenatal testing and perinatal genetics) Reproductive Genetics (includes preconception genetic services)

An integrative model for the comprehensive classification of BRCA1 and BRCA2 variants of uncertain clinical significance
ES Iverson et al, NPJ Genomic Medicine, June 3, 2022 (Posted: Jun 03, 2022 10AM)

We have developed functional assays and a statistical model called VarCall for classifying BRCA1 and BRCA2 VUS. Here we describe a multifactorial extension of VarCall, called VarCall XT, that allows for co–analysis of multiple forms of genetic evidence. We evaluated the accuracy of models defined by the combinations of functional, in silico protein predictors, and family data for VUS classification. VarCall XT classified variants of known pathogenicity status with high sensitivity and specificity, with the functional assays contributing the greatest predictive power

The Routine Failure to Clinically Identify Monogenic Cases of Common Disease in Clinical Practice: Addressing Diagnostic Misattributions and Errors
CDC Public Health Genomics Webinar, August 25, 2022 (Posted: May 25, 2022 11AM)

Changes in clinical and laboratory practice are needed to improve the diagnosis of monogenic forms of common diseases. This webinar seeks to focus attention on the need for universal genetic testing in common diseases for which the recommended clinical management of patients with specific monogenic forms of disease diverges from standard management and has evidence for improved outcomes. The speakers will review evidence from genomic screening of large patient cohorts, which has confirmed that monogenic case identification failures are commonplace in routine clinical care. These case identification failures constitute diagnostic misattributions-even diagnostic errors- where the care of individuals with monogenic disease defaults to the treatment plan offered to those with polygenic or non-genetic forms of the disease. The number of identifiable and actionable monogenic forms of common diseases is increasing with time.

Using Implementation Science Frameworks in Genomics and Precision Medicine: We Can Do Better!
M Clyne et al, CDC blog post, May 24, 2022 Brand (Posted: May 25, 2022 7AM)

A recent scoping review identified many structured approaches to the implementation of genomics and precision medicine and limited use of implementation science frameworks. As the number of evidence-based genomic applications increases in the next decade, an important challenge facing us is how to build the national, state, community and health systems research and evaluation infrastructure for using principles of implementation science in genomic medicine. The ultimate success of genomic medicine in improving health will depend on it.

The first complete human genome
JT Lovell et al, Nature, May 23, 2022 (Posted: May 24, 2022 8AM)

Sequences of the human genome have typically included gaps in repetitive regions of DNA. A combination of state-of-the-art technologies has now enabled researchers to generate the first complete human genome sequence.

A unique service: how an embedded psychology team can help patients and genetics clinicians within a clinical genetics service
C Firth et al, EJHG, May 16, 2022 (Posted: May 16, 2022 8AM)

There are many advantages to having an embedded psychology service both for patients and genetics clinicians, such as good opportunities for liaising around referrals and conducting joint clinical sessions, as well as being easily able to identify psychological training needs. Clinical psychologists can play a highly integral and essential role in the provision of psychosocial support for clinical genetics teams and provide an overview of the first such integrated clinical psychology service within clinical genetics in the United Kingdom.

Genomic architecture of fetal central nervous system anomalies using whole-genome sequencing
Y Yang et al, NPJ Genomic Medicine, May 13, 2022 (Posted: May 14, 2022 11AM)

162 fetuses with 11 common CNS anomalies were enrolled in this study. Primary diagnosis was achieved in 62 cases, with an overall diagnostic rate of 38.3%. Causative variants included 18 aneuploids, 17 CNVs, three small CNVs, and 24 SNVs. Among the 24 SNVs, 15 were novel mutations not reported previously. Furthermore, 29 key genes of diagnostic variants and critical genes of pathogenic CNVs were identified, including five recurrent genes: i.e., TUBA1A, KAT6B, CC2D2A, PDHA1, and NF1. Diagnostic variants were present in 34 (70.8%) out of 48 fetuses with both CNS and non-CNS malformations, and in 28 (24.6%) out of 114 fetuses with CNS anomalies only.

Using genomics to improve drug prescribing
L Blackburn, PHG Foundation, April 2022 (Posted: May 12, 2022 10AM)

Some pharmacogenomic testing is already available. An NHS England pharmacogenetics test evaluation working group reviews evidence for the potential inclusion of new pharmacogentic tests in the National Genomic Medicine Test Directory. The report identified a number of barriers towards wider adoption of pharmacogenomic tests, including making the most of research evidence, poor availability of tests, health professional education and engagement, and making pharmacogenomic information readily available, for example through electronic systems.

The current state of adult metabolic medicine in the United States: Results of a nationwide survey
JI Gold et al, Genetics in Medicine, May 10, 2022 (Posted: May 11, 2022 8AM)

The survey was completed by 91 providers from 73 institutions. Most adult patients with IMDs receive lifelong care from a single metabolic clinician, predominantly in pediatric clinic settings. The survey demonstrates the paucity of clinical resources dedicated to adult metabolic medicine. Care is fragmented and varies by medical system. Interest in HCT is robust but would benefit from standardized practices. Our findings reinforce the need for greater focus on adult metabolic medicine in the United States.

The Gene Curation Coalition: A global effort to harmonize gene–disease evidence resources
MT DiStephano et al, Genetics in Medicine, May 4, 2022 (Posted: May 04, 2022 9AM)

On the basis of 241 survey responses from the genetics community, a consensus term set was chosen for grading gene–disease validity and database submissions. As of December 2021, the database contained 15,241 gene–disease assertions on 4569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene–disease validity ranged from 5.3% to 13.4%.

The final pieces of the human genome
M Attwaters, Nature Rev Genetics, April 29, 2022 (Posted: Apr 29, 2022 0PM)

Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer
A Vanderstichel et al, NPJ Genomic Medicine, April 28, 2022 (Posted: Apr 29, 2022 0PM)

We confirmed that nucleosome scores were elevated in invasive carcinoma patients, but not in patients with benign or borderline disease. Combining nucleosome scores with chromosomal instability scores assessed in the same cfDNA improved prediction of malignancy. Nucleosome scores were, however, more reliable to predict non-high-grade serous ovarian tumors, which are characterized by low chromosomal instability. These data highlight that compared to chromosomal instability, nucleosome footprinting provides a complementary and more generic read-out for pre-surgical diagnosis of invasive disease in women with adnexal masses.

Returning individual research results in international direct-to-participant genomic research: results from a 31-country study
M Lang et al, EJHG, April 28, 2022 (Posted: Apr 28, 2022 0PM)

This paper summarizes the results of a 31-country qualitative study of expert perspectives on the regulation of international “direct-to-participant” (DTP) genomic research. We outline how the practice of directly recruiting participants for genomic studies online complicates ethics and regulatory considerations for the return of individual research results.

Structured approaches to implementation of clinical genomics: A scoping review
HL Brown et al, Genetics in Medicine, April 20, 2022 (Posted: Apr 21, 2022 4PM)

This scoping review identified a significant number of structured approaches developed to inform the implementation of genomic medicine into clinical practice, with limited use of implementation science to support the process. We recommend the use of existing implementation science theory and the expertise of implementation scientists to inform the design of genomic programs being implemented into clinical care.

Best practices for the interpretation and reporting of clinical whole genome sequencing
CAA Tse et al, NPJ Genomic Medicine, April 8, 2022 (Posted: Apr 09, 2022 2PM)

Whole genome sequencing (WGS) shows promise as a first-tier diagnostic test for patients with rare genetic disorders. However, standards addressing the definition and deployment practice of a best-in-class test are lacking. To address these gaps, the Medical Genome Initiative, a consortium of leading health care and research organizations in the US and Canada, was formed to expand access to high quality clinical WGS by convening experts and publishing best practices. Here, we present best practice recommendations for the interpretation and reporting of clinical diagnostic WGS.

No April fools in clinical genomics
A McNeil, EJHG, April 7, 2022 (Posted: Apr 07, 2022 10AM)

Emerging precision diagnostics in advanced cutaneous squamous cell carcinoma
G Geidel et al, NPJ Genomic Medicine, March 23, 2022 (Posted: Mar 25, 2022 7AM)

Advanced cutaneous squamous cell carcinoma (cSCC) encompasses unresectable and metastatic disease. Although immune checkpoint inhibition has been approved for this entity recently, a considerable proportion of cases is associated with significant morbidity and mortality. Clinical, histopathological, and radiological criteria are used for current diagnostics, classification, and therapeutic decision-making. This article highlights new insights into the mutational profile of cSCC, summarizes current diagnostic and therapeutic standards, and discusses emerging diagnostic approaches with emphasis on liquid biopsy and tumor tissue-based analyses.

Resource Tool Kit
ACMG, Medical Genetics Awareness Week, March 2022 (Posted: Mar 23, 2022 8AM)

Welcome to our Medical Genetics Awareness Week Resource Tool Kit. On this page you will find resources and tools to help you in your annual celebration of the important work of clinical and laboratory geneticists, genetic counselors, genetic nurses and physician assistants, and so many others devoted to translating genes into health.


Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.