Dysferlin deficiency: the cause of limb-girdle muscular dystrophy 2B and Miyoshi myopathy in a Chinese pedigree / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To identify an inbred Chinese pedigree with autosomal recessive muscular dystrophy and analyze the molecular defects.</p><p><b>METHODS</b>Linkage analysis was conducted using short tandem repeat(STR) markers from the regions associated with limb-girdle muscular dystrophy type 2A(LGMD2A) through 2H. Multi-Western blot was performed with anti-calpain-3, anti-dysferlin, anti-gamma-sarcoglycan, anti-alpha-sarcoglycan, and anti-dystrophin monoclonal antibodies. Mutation was determined by reverse transcriptase-polymerase chain reaction and sequencing.</p><p><b>RESULTS</b>Two-point linkage analysis showed significant Lod scores with markers from chromosome 2p13, the highest two-point Lod scores were obtained with D2S337 (Z(max)=1.86 at theta=0). Multi-Western blot confirmed dysferlin deficiency of muscle specimen from the proband. Mutation analysis revealed a novel 6429delG mutation on exon 53 of the DYSF gene for the proband.</p><p><b>CONCLUSION</b>The authors identified an inbred Chinese pedigree with Miyoshi myopathy caused by a 6429delG on the DYSF gene. This mutation is predicted to result in premature termination of translation.</p>