Beta myosin heavy chain and myosin binding protein C gene double mutation in hypertrophic cardiomyopathy with a malignant phenotype
█ Case report
Nagy Viktória1, Pálinkás Attila2, Tringer Annamária1, Lidia Hategan1, Csányi Beáta1, Pálinkás Eszter1, Borbás János1, Hegedűs Zoltán3,4, Nagy István5,6, Sepp Róbert1
1Szegedi Tudományegyetem, II. sz. Belgyógyászati Klinika és Kardiológiai Központ, Szeged
2Erzsébet Kórház, Hódmezővásárhely
3Biofizikai Intézet, Szegedi Biológiai Központ, Szeged
4Pécsi Tudományegyetem, Biokémiai és Orvosi Kémiai Intézet, Pécs
5Biokémiai Intézet, Szegedi Biológiai Központ, Szeged
6Seqomics Biotechnológiai Kft., Mórahalom
Background: Hypertrophic cardiomyopathy (HCM) is a primary disease of the myocardium, caused by mutations in sarcomeric genes. Patients may carry more than one causative mutation, which leads to more severe disease.
Patients and methods: We report the results of genetic analysis of a family where both parents suffered from HCM. The mother was diagnosed having HCM at the age of 12, characterized by typical asymmetric hypertrophy (septal thickness: 21 mm). Although risk stratification didn’t indicate high risk for sudden cardiac death, she died suddenly at the age of 32. The father’s illness became known at age of 37 in the form of non-obstructive HCM with septal hypertrophy of 22 mm. HCM in of one of their sons was known since the age of 2, as non-obstructive HCM with a septal thickness of 22 mm, with diastolic dysfunction. He died of progressive biventricular heart failure when he was 13. Genetic analysis was performed in the family with targeted resequencing of 103 known causative cardiomyopathy genes.
Results: Genetic analysis revealed two causative sarcomeric gene mutations in the family. One of them affected the beta myosin heavy chain gene (MYH7 p.Arg719Gln) while the other affected the myosin binding protein C gene (MYBPC3 p.Ser593ProfsTer11). The mother carried the MYH7 p.Arg719Gln mutation the father carried the MYBPC3 p.Ser593ProfsTer11 mutation, while their son, affected by the most severe form of the disease, carried both of the mutations.
Conclusion: Double mutation affecting the two most important sarcomeric genes is the most likely explanation for the malignant disease in the son, characterized by progressive disease and early death.