Unique Genetic Profiles in Hypertrophic Cardiomyopathy Patients From São Miguel Island (Azores, Portugal)

• 全文链接
• 请求原文

作   者：

Duarte, Fabiana;  Oliveira, Luis;  Baixia, Marcia;  Mota-Vieira, Luisa;  Machado, Carina; 

作者机构：

University of Lisbon Faculty of Sciences;  EPER;  Univ Porto; 

关键词：

novel mutations;  genotype–phenotype;  hypertrophic cardiomyopathy;  Azores;  genotype-phenotype;  sarcomeric genes; 

期刊名称：

Clinical Genetics

i s s n：

0009-9163

年卷期：

2025 年 107 卷 4 期

页   码：

434-440

页   码：

摘   要：

To investigate the clinical features and mutational spectrum underlying hypertrophic cardiomyopathy (HCM) in S & atilde;o 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.