OBJECTIVES: We studied the clinical and genetic features of @entity1121 ( @entity1121 ) caused by mutations in the myosin-binding protein C gene ( @entity18963 ) in 110 consecutive, unrelated @entity1 and family members of European descent. BACKGROUND: Mutations in the @entity18963 gene represent the cause of @entity1121 in approximately 15% of familial cases. @entity18963 mutations were reported to include mainly nonsense versus missense mutations and to be characterized by a delayed onset and benign clinical course of the disease in Japanese and French families. We investigated the features that characterize @entity18963 variants in a large, unrelated cohort of consecutive @entity1 . METHODS: The @entity18963 gene was screened by single-strand conformational polymorphism analysis and sequencing. The clinical phenotypes were analyzed using rest and 24-h electrocardiography, electrophysiology, two-dimensional and Doppler echocardiography and angiography. RESULTS: We identified 13 mutations in the @entity18963 gene: one nonsense, four missense and three splicing mutations and five small deletions and insertions. Of these, 11 were novel, and two were probably founder mutations. @entity1 with @entity18963 mutations presented a broad range of phenotypes. In general, the 16 carriers of protein truncations had a tendency toward earlier disease manifestations (33 +/- 13 vs. 48 +/- 9 years; p = 0.06) and more frequently needed invasive procedures (septal ablation or cardioverter-defibrillator implantation) compared with the 9 carriers of missense mutations or in-frame deletions (12/16 vs. 1/9 @entity1 ; p < 0.01). CONCLUSIONS: Multiple mutations, which include missense, nonsense and splicing mutations, as well as small deletions and insertions, occur in the @entity18963 gene. Protein truncation mutations seem to cause a more severe disease phenotype than missense mutations or in-frame deletions.

Spectrum of clinical phenotypes and gene variants in cardiac myosin-binding protein C mutation carriers with XXXX .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity1121 :: ('MESH:D002312', 'Disease') :: ['HCM', 'hypertrophic cardiomyopathy'] @entity18963 :: ('4607', 'Gene') :: ['MYBPC3']
@entity1121 :: (MESH:D002312,Disease) :: ['hypertrophic cardiomyopathy']
