Purpose: We performed genetic analysis of Hungarian patients with HCM using next-generation sequencing.
Patient and methods: We examined 103 patients with HCM (58 men, 45 women, average age: 45±15 years). Familial disease was detected in 27 cases (26%). Maximal left ventricular (LV) wall thickness was 22±6 mm and significant LV outflow tract gradient was observed in 28 cases. Using next-generation sequencing we screened 103 known causative cardiomyopathy genes.
Results: Genetic analysis identified 284 rare (<1% minor allele frequency) potentially causative variants, causing either amino acid change of affecting the ’splice site’ region. Pathogenic or likely pathogenic variants were identified in 68 patients (66%). Pathogenic variants most commonly affected the MYBPC3 gene (36/103, 35%), the MYH7 gene (16/103, 16%), and the TNNT2 and TPM1 genes (3/103, 3%). Rare sarcomeric gene variants, affecting the TNNI3 gene (2/103, 2%), the ACTC1, MYL2 and MYL3 genes (1/103, 1%) has also been detected. We observed the MYBPC3 p.Gln1233*, p.Pro955fs and p.Ser593fs variants in multiple cases (8, 5 and 6 cases, respectively) pointing out to a possible founder effect.
Discussion: Next-generation sequencing is appropriate for screening high number of patients. In accordance with literature data, the MYBPC3 gene seems to be the most commonly affected gene in Hungarian HCM patients.