First report of a novel LMNA mutation in a Chinese family with limb-girdle muscular dystrophy

LMNA gene encodes the ubiquitous protein lamin A/C, which is a component of the fibrous meshwork of intermediate filaments located at the inner surface of the nuclear envelope (Worman 2012). Lamin A/C are splicing variants encoded by the LMNA gene and share the first 566 amino acids. Mutations in LMNA gene are recently known to be responsible for more than 10 different clinical syndromes, most of which show overlapping features. Worman and Bonne (2007) classified the disorders into four major types: diseases of skeletal and cardiac muscle, lipodystrophy syndromes, peripheral neuropathy and premature ageing. Of the skeletal and cardiac muscles types, limb–girdle muscular dystrophy type 1B (LGMD1B), autosomal dominant Emery–Dreifuss muscular dystrophy 2 (EDMD2) and dilated cardiomyopathy 1A (CMD1A) are common (Capell and Collins 2006). Among the muscle type disorders related to LMNA gene mutations, LGMD1B is slowly progressive, with age-related atrioventricular cardiac conduction disturbance, dilated cardiomyopathy, muscle weakness and the absence of early contractures. However, EDMD2 is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and cardiomyopathywith a variable degree of conduction system disease (Capell and Collins 2006). In this report, we characterized a large Chinese family with atrioventricular block (AVB) as the most prominent feature, with concomitant moderate pelvic limb skeletal muscle defects. Due to the medical history, clinical manifestations and neurological/cardiological examinations, this family was diagnosed with autosomal LGMD1B. Then, a mutation