Highlights
Inequity of genetic screening: DNA tests fail non-white families more often
From the article: "DNA sequencing for metabolic diseases in newborns may eventually replace the traditional method of genetic screening used to check all new babies for a group of rare, inherited diseases that can cause severe neurologic damage and death if not detected quickly. But currently, research is showing that those advanced methods of genetic tests aren't equally useful for everyone: They're less accurate for non-white families, raising concerns about how historical gaps in whose DNA gets studied produce inequities in medical care."
Challenges and opportunities for Lynch syndrome cascade testing in the United States.
Lauren E Passero et al. Fam Cancer 2024 3
From the abstract: " Lynch syndrome is an underdiagnosed genetic condition that increases lifetime colorectal, endometrial, and other cancer risk. Cascade testing in relatives is recommended to increase diagnoses and enable access to cancer prevention services, yet uptake is limited due to documented multi-level barriers. Individual barriers such as feelings of fear, guilt, and anxiety and limited knowledge about Lynch syndrome as well as interpersonal barriers including complex family dynamics and language barriers limit family communication about Lynch syndrome and prevent uptake of genetic screening for relatives. Organizational and environmental barriers including a shortage of genetics professionals, high costs, and fears of discrimination also reduce cascade testing. These multi-level barriers may disproportionately impact underserved populations in the United States,"
Newborn Screening for Inborn Errors of Metabolism by Next-Generation Sequencing Combined with Tandem Mass Spectrometry
C Tang et al, IJNS, March 2024
From the abstract: " We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. "
Combining rare and common genetic variants improves population risk stratification for breast cancer
A Bolze et al, Genetics in Medicine Open, February 2, 2024
From the abstract: " This study aimed to evaluate the performance of different genetic screening approaches to identify women at high-risk of breast cancer in the general population. We retrospectively studied 25,591 women with available electronic health records and genetic data, participants in the Healthy Nevada Project. Family history of breast cancer was ascertained on or after the record of breast cancer for 78% of women with both, indicating that this risk assessment method is not being properly utilized for early screening. Genetics offered an alternative method for risk assessment. 11.4% of women were identified as high-risk based on possessing a predicted loss-of-function (pLOF) variant in BRCA1, BRCA2 or PALB2 (hazard ratio = 10.4, 95% confidence interval: 8.1-13.5), or a pLOF variant in ATM or CHEK2 (HR = 3.4, CI: 2.4-4.8), or being in the top 10% of the polygenic risk score (PRS) distribution (HR = 2.4, CI: 2.0-2.8). "
