BACKGROUND: Small selected cohort studies suggest that mutations in the cardiac myosin binding protein-C ( @entity18963 ) gene cause late-onset, clinically benign @entity1121 ( @entity1121 ). The aim of this study was to test this hypothesis in a large series of families with @entity1121 associated with @entity18963 mutations. METHODS AND RESULTS: The initial study population comprised 57 probands with 42 mutations (26 [61.9%] novel) in @entity18963 . Missense mutations (15, 45.6%) were the most frequent, and multiple mutations occurred in 4 (7.0%) probands. Another 110 mutation carriers were identified during familial evaluation; 38 were clinically affected with @entity4346 >= 13 mm. Disease penetrance was, therefore, incomplete (56.9% in all mutation carriers, 34.5% in relatives), related to age (38.4% <40 versus 68.6% >= 40 years, P<0.001), and was greater in males than females (65.1% versus 48.1%, P=0.03). In 9 families (25 individuals) with the @entity23664 mutation, there was marked heterogeneity in age at diagnosis (5 to 80 years), pattern of @entity1184 (11 none, 9 asymmetrical, 3 concentric, 1 apical, 1 eccentric), and prognosis (premature @entity944 in 2 individuals compared with survival to advanced age in 6 individuals). During follow up of 7.9+/-4.5 years, in 82 clinically affected individuals the annual risk of @entity944 and all cause mortality was 0.46% and 0.93% per year, respectively. CONCLUSIONS: Disease expression in families with @entity1121 related to @entity18963 mutations shows marked heterogeneity with incomplete, age-related, and gender specific penetrance. Importantly, complex genetic status is observed and should be considered when mutation analysis and cascade screening is used in the evaluation of at risk family members.

Cardiac myosin binding protein-C mutations in families with XXXX : disease expression in relation to age, gender, and long term outcome.

@entity23664 :: ('p|SUB|R|502|W', 'ProteinMutation') :: ['R502W'] @entity944 :: ('MESH:D003645', 'Disease') :: ['sudden death'] @entity1184 :: ('MESH:D006984', 'Disease') :: ['hypertrophy'] @entity18963 :: ('4607', 'Gene') :: ['MYBPC3'] @entity4346 :: ('MESH:D017379', 'Disease') :: ['left ventricular hypertrophy'] @entity1121 :: ('MESH:D002312', 'Disease') :: ['HCM', 'hypertrophic cardiomyopathy']
@entity1121 :: (MESH:D002312,Disease) :: ['hypertrophic cardiomyopathy']
