The following is a summary of “French hypertrophic cardiomyopathy gene register: A systematic large gene screening for hypertrophic cardiomyopathy,” published in the September 2024 issue of Cardiology by Hagège et al.
Researchers conducted a retrospective study testing the performance of this approach in GEREMY, an observational French r+egister for hypertrophic cardiomyopathy (HCM).
They initially screened 12-gene panels, which included the Fabry disease (GLA) and transthyretin (TTR) genes. If the negative results matched the clinical profile, 17–80 gene panels were used.
The results showed 748 adults, 68.9% male, an average age of 54.6 ± 18.1 years, 27.5% with a family history of HCM, and a maximum wall thickness of 19.1 ± 4.8 mm. Pathogenic or likely pathogenic variants were detected in 296 (39.6%), 233 were in sarcomeric genes, with MYBPC3 (150) and MYH7 (42) frequent, and 24 variants were identified, including 8 patients with multiple variants. Additionally, 63 variants were found in non-sarcomeric genes, with 26 only detected by large panels, mainly TTR (26) and GLA (9), representing 8.8% and 3.0% of positive results. Detection rates were 57.1% for individuals under 40 and 68.6% with a family history of HCM, then 28.7% and 26.1% for others (P<0.001), 148 had variants of unknown significance, and 95 had senile or AL amyloidosis in patients with negative results.
They concluded that systematic genetic screening with a limited panel showed good performance, with diagnosis of Fabry disease (~1 %) and hereditary TTR amyloidosis (~3.5 %), but larger targeted panels were more conclusive in 35.3 % of patients, of which 12 % had a negative initial approach.
Source: sciencedirect.com/science/article/abs/pii/S0167527324011641
