AUTHOR=Franke Magda , Książczyk Tomasz Marcin , Dux Marta , Chmielewski Przemysław , Truszkowska Grażyna , Czapczak Dorota , Pietrzak Radosław , Bilinska Zofia Teresa , Demkow Urszula , Werner Bożena 

TITLE=A MYH7 variant in a five-generation-family with hypertrophic cardiomyopathy

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1306333

DOI=10.3389/fgene.2024.1306333

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Hypertrophic cardiomyopathy (HCM) is a genetic condition with a prevalence of 1:500–1:3 000. Variants in genes encoding sarcomeric proteins are mainly responsible for the disease. <italic>MYH7</italic> gene encoding a myosin heavy chain beta, together with <italic>MYPBC3</italic> gene are the two most commonly affected genes. The clinical presentation of this disease varies widely between individuals. This study aims to report a variant of <italic>MYH7</italic> responsible for HCM in a five-generation family with a history of cardiac problems.</p><p><bold>Methods:</bold> The diagnosis was established according to the European Society of Cardiology HCM criteria based on two-dimensional Doppler echocardiography or cardiovascular magnetic resonance. Genetic analysis was performed using next-generation-sequencing and Sanger method.</p><p><bold>Results:</bold> The medical history of the presented family began with a prenatal diagnosis of HCM in the first child of a family with previously healthy parents. Five generations of the family had a long history of sudden cardiac death and cardiac problems. A NM_000257.4:c.2342T&gt;A (p.Leu781Gln) variant was detected in the MYH7 gene. It was heterozygous in the proband and in all affected individuals in a large family. The variant was present in 10 affected members of the family, and was absent in 7 members. The clinical course of the disease was severe in several members of the family: three family members died of sudden cardiac death, one patient required heart transplantation, three underwent septal myectomy, and three required implantable cardioverter defibrillator (ICD) implantation.</p><p><bold>Conclusion:</bold> Herein, we report a <italic>MYH7</italic> variant responsible for HCM. Familial HCM is inherited primarily in autosomal dominant mode, which is in accordance with our study. However, the presented family showed a broad clinical spectrum of HCM. Out of 10 family members with positive genetic testing 8 had severe presentation of the disease and 2 had a mild phenotype. This suggests that the severity of the disease may depend on other factors, most likely genetic.</p>