AI Article Synopsis
- The study aims to investigate cardiovascular diseases with genetic roots, specifically RASopathies and Marfan syndrome, using DNA data from large biobanks.
- Researchers conducted exome sequencing on subjects, identifying variants linked to these conditions and revealing that many individuals had genetic markers without a formal diagnosis.
- Findings highlighted that a significant number of those with genetic variants show symptoms consistent with these syndromes but don't meet formal diagnostic criteria, suggesting the need for routine genetic screening to improve patient care and prevent severe health issues.
Article Abstract
Purpose: The purpose of this study is to use a genotype-first approach to explore highly penetrant, autosomal dominant cardiovascular diseases with external features, the RASopathies and Marfan syndrome (MFS), using biobank data.
Methods: This study uses exome sequencing and corresponding phenotypic data from Mount Sinai's BioMe (n = 32,344) and the United Kingdom Biobank (UKBB; n = 49,960). Variant curation identified pathogenic/likely pathogenic (P/LP) variants in RASopathy genes and FBN1.
Results: Twenty-one subjects harbored P/LP RASopathy variants; three (14%) were diagnosed, and another 46% had ≥1 classic Noonan syndrome (NS) feature. Major NS features (short stature [9.5% p = 7e-5] and heart anomalies [19%, p < 1e-5]) were less frequent than expected. Prevalence of hypothyroidism/autoimmune disorders was enriched compared with biobank populations (p = 0.007). For subjects with FBN1 P/LP variants, 14/41 (34%) had a MFS diagnosis or highly suggestive features. Five of 15 participants (33%) with echocardiographic data had aortic dilation, fewer than expected (p = 8e-6). Ectopia lentis affected only 15% (p < 1e-5).
Conclusions: Substantial fractions of individuals harboring P/LP variants with partial or full phenotypic matches to a RASopathy or MFS remain undiagnosed, some not meeting diagnostic criteria. Routine population genotyping would enable multidisciplinary care and avoid life-threatening events.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796917 | PMC |
| http://dx.doi.org/10.1038/s41436-020-00973-2 | DOI Listing |
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