Abstract
BackgroundLimb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, the incidence of LGMD2C in Japanese has been unknown because the genetic background remains uncharacterized in many patients clinically diagnosed with DMD.MethodsWe enrolled 324 patients referred to the Kobe University Hospital with suspected DMD. Mutations in the dystrophin or the SGCG genes were analyzed using not only genomic DNA but also cDNA.ResultsIn 322 of the 324 patients, responsible mutations in the dystrophin were successfully revealed, confirming DMD diagnosis. The remaining two patients had normal dystrophin expression but absence of γ-sarcoglycan in skeletal muscle. Mutation analysis of the SGCG gene revealed homozygous deletion of exon 6 in one patient, while the other had a novel single nucleotide insertion in exon 7 in one allele and deletion of exon 6 in the other allele. These mutations created a stop codon that led to a γ-sarcoglycan deficiency, and we therefore diagnosed these two patients as having LGMD2C. Thus, the relative incidence of LGMD2C among Japanese DMD-like patients can be calculated as 1 in 161 patients suspected to have DMD (2 of 324 patients = 0.6%). Taking into consideration the DMD incidence for the overall population (1/3,500 males), the incidence of LGMD2C can be estimated as 1 per 560,000 or 1.8 per million.ConclusionsTo the best of our knowledge, this is the first study to demonstrate a low incidence of LGMD2C in the Japanese population.
Highlights
Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD)
Limb-girdle muscular dystrophy type 2C (LGMD2C) (OMIM # 253700) is an autosomal recessive disorder caused by mutations in the SGCG gene, which encodes γsarcoglycan
Patients Boys were enrolled in this cohort if they had been referred to the Kobe University Hospital with a tentative clinical DMD diagnosis based on strongly elevated levels of serum creatine kinase (CK) activity
Summary
Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). DMD is caused by a mutation in the dystrophin gene on the short arm of the X chromosome and is characterized by the absence of dystrophin in skeletal muscle Those affected by DMD develop muscle weakness by the age of 4 or 5, followed by progressive muscle wasting that leads to patients being wheelchair bound by the age of 12. Limb-girdle muscular dystrophy type 2C (LGMD2C) (OMIM # 253700) is an autosomal recessive disorder caused by mutations in the SGCG gene, which encodes γsarcoglycan It is characterized by a childhood onset of progressive muscular dystrophy. Calf hypertrophy and lumbar lordosis are common [2] Based on these clinical findings, LGMD2C is referred to as a severe childhood autosomal recessive muscular dystrophy or as a Duchenne muscular dystrophy (DMD)-like autosomal recessive disease [3]
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