Key result
Genetic analysis of Azorean HCM patients identifies seven disease-causing variants including novel MYBPC3 deletions.
Why the study?
The clinical features and mutational spectrum underlying hypertrophic cardiomyopathy in São Miguel Island had not been characterized.
Observational (n=37)
No
This first molecular and clinical analysis of HCM in the Azores identified novel genetic variants, including a homozygous TNNT2 variant associated with a stable clinical course, challenging the belief that homozygous variants always predict a worse prognosis.
To investigate the clinical features and mutational spectrum underlying hypertrophic cardiomyopathy (HCM) in São Miguel Island (Azores, Portugal), we analyzed 37 adult patients (12 sporadic, 25 familial) with positive genetic tests. Seven disease-causing variants were identified, being two novels, in three sarcomeric genes (MYH7, TNNT2, and MYBPC3) and one non-sarcomeric gene (ALPK3). The novel variants, classified as likely pathogenic (LP), involved large multi-exon deletions in MYBPC3 (exons 26-32 and 28-33). These deletions were found in heterozygosity in two young males who remained clinically stable, though early onset may predict a more severe prognosis. Segregation analysis in a consanguineous family revealed two new genotypes: a digenic heterozygous for MYH7:c.1750G>C (p.Gly584Arg; P) and TNNT2:c.842A>T (p.Asn281Ile; LP) variants, and a homozygous for the TNNT2 variant. The 70-year-old homozygous patient remained stable and without arrhythmic events, challenging the belief that homozygous variants have a worse prognosis. This study is the first molecular and clinical analysis of HCM in the Azores.
No takes yet. Share an insight, caveat, or question.
Duarte et al. (2024) conducted an observational in Hypertrophic cardiomyopathy (n=37). Genetic profiling was evaluated on Identification of disease-causing variants and clinical features. Genetic analysis of 37 adult HCM patients in the Azores identified seven disease-causing variants, including two novel large multi-exon deletions in MYBPC3.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: