DYSF mutation analysis in a group of Chinese patients with dysferlinopathy

Abstract

Objective

Dysferlinopathies belong to heterogeneous group of autosomal recessive muscular disorders caused by mutations in the gene encoding dysferlin. The classifications of the dysferlinopathies mainly include limb-girdle muscular dystrophy 2B (LGMD2B) with predominantly proximal weakness, Miyoshi myopathy (MM) with calf muscle weakness and atrophy, and distal myopathy with anterior tibial onset (DMAT) with tibialis muscle atrophy. We describe the genetic character of dysferlinopathies in a group of Chinese patients.

Methods

DYSF mutations screening were done after muscle biopsy and immunohistochemical staining.

Results

Eight patients showed an absence or drastic decrease of dysferlin expression in biopsied muscle. We identified 6 different mutations, including one nonsense mutation, two insertion mutation, two deletion mutations and one splice site mutation. Five of them were novel mutations.

Conclusion

We described 8 Chinese patients with dysferlinopathy (four had a distal phenotype of MM; one had a phenotype of DMAT and three presented with LGMD2B). It is the first report of genetic confirmed DMAT in China. Mutations c.3112C>T and c.1045dup, may be recurrent mutations in China.

Introduction

Dysferlin is a 230 kDa transmembrane protein and has been shown to be involved in the process of membrane repair [1], myoblast differentiation [2], T tubulogenesis [3] and muscle regeneration [4] through mechanisms of membrane organisation. Dysferlinopathies refer to a group of autosomal recessive muscular dystrophies caused by mutations in DYSF. Mutations in DYSF lead to different clinical phenotypes of muscular dystrophy according the distribution of affected muscles. It encompasses limb-girdle muscular dystrophy (LGMD2B), Miyoshi myopathy (MM), distal myopathy with anterior tibial onset (DMAT), isolated hyperCK and rigid spine syndrome. LGMD2B is characterized by predominant weakness and atrophy of muscles of the pelvic and shoulder girdle, onset in the late teens or later. LGMD2B is the second more frequent form of LGMD in Western countries [5] and Japan [6]. In China, LGMD has not been adequately studied, and its epidemiology remains unclear. MM is an early-adult onset, distal muscular dystrophy, characterized by predominant involvement in the calf muscles [7]. DMAT is a distal muscular dystrophy, characterized by predominant involvement in the anterior compartment group [8]. There are very few reports regarding dysferlinopathy in the Chinese population. In this study, we performed mutation analysis of DYSF in 8 Chinese patients with a dysferlin protein deficiency; the clinical and pathological features were collected and analyzed.