title: Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD.
abstract: BACKGROUND
  Limb-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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  In 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 gamma-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 gamma-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.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first study to demonstrate a low incidence of LGMD2C in the Japanese population.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Okizuka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Awano
authors.forename: Koichi
authors.initials: K
authors.lastname: Maruyama
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kumagai
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator; D016189:Dystrophin / Q000235:genetics; D005091:Exons; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D049288:Muscular Dystrophies, Limb-Girdle / Q000453:epidemiology / Q000235:genetics*; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D049031:Sarcoglycans / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D016189:Dystrophin; C526573:SGCG protein, human; D049031:Sarcoglycans