Mutation in the CAV3 gene causes partial caveolin-3 deficiency and persistent elevated levels of serum creatine kinase

Abstract

Mutations in the caveolin-3 (CAV3) gene are associated with autosomal dominant limb-girdle muscular dystrophy (LGMD1C). The authors report a novel sporadic mutation in the CAV3 gene in two unrelated children with persistent elevated levels of serum creatine kinase (hyperCKemia) without muscle weakness. Immunohistochemistry and quantitative immunoblot analysis of caveolin-3 showed reduced expression of the protein in muscle fibers. Our data indicate that a partial caveolin-3 deficiency should be considered in the differential diagnosis of idiopathic hyperCKemia.

Caveolinopathies: from the biology of caveolin-3 to human diseases

“…No other Caveolin-3 and muscle diseases E Gazzerro et al myopathic features were evident. 62,63 Similar clinical features were reported in H-CK (s) patients identified in later studies (Table 2).…”

“…Cav-3 protein is 151 amino acids (aa) long and is divided in five separate domains: N-terminal (aa 1-53), scaffolding (aa [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73], transmembrane (aa 74-106), and C-terminal (aa 107-151). The N-terminal domain contains a signature sequence (aa 41-48, FED-VIAEP) that is present in all caveolins.…”

“…Of the 11 individuals with the confirmed mutation, three exhibited both RMD and LGMD-1C features, two had predominantly LGMD1C characteristics, two, both minors, had muscle stiffness only, and one was asymptomatic. 62 Likewise, Fischer et al 61 described family members with different, but overlapping, muscle disease phenotypes. RMD was evident in all 14 affected individuals.…”

“…62,79 Management of caveolinopathic patients Symptomatic supportive care aimed to preserve muscle function, maximize functional ability and treat complications is particularly important in those patients with LGMD. Weight control to avoid obesity, physical therapy and stretching exercises to promote mobility and prevent contractures, use of mechanical aids and social and emotional support must be provided.…”

Caveolin-3 T78M and T78K missense mutations lead to different phenotypes in vivo and in vitro

“…15 The relevance of Cav-3 in muscle physiology was further confirmed by the findings that mutations in the CAV3 gene result in distinct neuromuscular and cardiac disorders, such as limb girdle muscular dystrophy (LGMD) 1-C, idiopathic persistent elevation of serum creatine kinase (hyperCKemia), inherited rippling muscle disease (RMD), distal myopathy and familial hypertrophic cardiomyopathy (HCM). [16][17][18][19][20] The CAV3 gene (OMIM no. 601253) spans 12 kb of genomic DNA on chromosome 3p25 and contains two exons.…”