Mutation of V896M in cardiac myosin binding protein-c gene in two Chinese families with hypertrophic cardiomyopathy

Abstract

Abstract. To investigate the genotype-phenotype correlation in chinese familial and sporadic hypertrophic cardiomyopathy, specific exons of the myosin binding protein-c gene (MYBPC3) were screened in six families with hypertrophic cardiomyopathy (HCM; FHCM) and in 20 patients with sporadic HCM (SHCM) from the anhui Province region of china. The V896M mutation was detected for the first time in China in two families with FHCM. The mutation was not found in 100 healthy control subjects. No mutations of MYBPC3 were detected in any of the SHCM patients. In contrast to previous reports, the V896M mutation may be a disease-causing mutation in China, and exon 27 of MYBPC3 may be a mutational hotspot in FHCM patients. However, mutations of MYBPC3 were not prevalent among SHCM patients.

Exome Sequencing Identifies a Novel LMNA Splice-Site Mutation and Multigenic Heterozygosity of Potential Modifiers in a Family with Sick Sinus Syndrome, Dilated Cardiomyopathy, and Sudden Cardiac Death

“…In contrast to previous reports, our study does not support the role of TMPO p.Arg690Cys [ 22 ], MYBPC3 p.Val895Met [ 23 , 24 ], and HCN4 p.Met1113Val [ 25 ] as highly penetrant, primary mutations. We excluded TMPO p.Arg690Cys as the primary mutation in our family although this variant was implicated as a DCM mutation [ 22 ].…”

“…MYBPC3 mutations have been known to contribute hypertrophic cardiomyopathy (HCM); however, the role of the MYBPC3 p.Val895Met variant is not clear. As evidence for pathogenicity, pVal895Met was found in a single “white” patient [ 23 ] and five patients from two unrelated Chinese families [ 24 ]. The variant also was considered a potential modifier of HCM after it was found in a European HCM family with a second variant MYH7 A355T; one affected individual had only the MYH7 variant and three affected had both variants including one patient with a severe phenotype [ 26 ].…”

“…By WES studies, we found many potential modifiers that will require further analysis ( Table 2 ) including a novel TTN p.Thr6018Ser variant, the rare variants reported as putative mutations including TMPO p.Arg690Cys [ 22 ] and p. MYBPC3 Val895Met [ 23 , 24 , 26 ], and common variants including p. SCN5A His558Arg associated with increased risk for arrhythmia [ 52 ]. In addition, we found PKP4 p.Arg795Lys in all four affected members and in one unaffected member (III-2).…”

Identification of novel mutations including a double mutation in patients with inherited cardiomyopathy by a targeted sequencing approach using the Ion Torrent PGM system

“…This is associated with a poor prognosis, and explains why the proband exhibited an early onset malignant phenotype of HCM ( 50 ). As a mutation carrier, the proband's mother (A11) is a family member at risk who was clinically asymptomatic ( 51 ); long-term follow-up is therefore essential in this subject. However, her children are at high risk of developing HCM, and thus genetic testing may be particularly helpful in this group.…”

The Specifics of Hypertrophic Cardiomyopathy Clinical Presentation in Patients With Various Mutations of Sarcomere Genes

“…Замена Ser236Gly в работах ученых из Кореи, Япо-нии и Китая определена как диагностически значи-мая мутация для ГКМП [12,13]. Китайские исследо-ватели назвали сайт 236 "горячей точкой", т. к. мута-ция Ser236Gly была выявлена у 3 пациентов из 100 (3,0%).…”