Low Incidence of Limb-girdle Muscular Dystrophy Type 2C Revealed by a Mutation Study in Japanese Patients Clinically Diagnosed with DMD

Overview

Journal BMC Med Genet

Publisher Biomed Central

Specialty Genetics

Date 2010 Mar 31

PMID 20350330

Citations 2

Authors

Yo Okizuka

Yasuhiro Takeshima

Kyoko Itoh

Zhujun Zhang

Hiroyuki Awano

Koichi Maruyama

Toshiyuki Kumagai

Mariko Yagi

Masafumi Matsuo

Affiliations

Soon will be listed here.

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.

Citing Articles

A Journey with LGMD: From Protein Abnormalities to Patient Impact.

Georganopoulou D, Moisiadis V, Malik F, Mohajer A, Dashevsky T, Wuu S Protein J. 2021; 40(4):466-488.

PMID: 34110586 PMC: 8190568. DOI: 10.1007/s10930-021-10006-9.

Mutational spectrum of autosomal recessive limb-girdle muscular dystrophies in a cohort of 112 Iranian patients and reporting of a possible founder effect.

Mojbafan M, Bahmani R, Dabbagh Bagheri S, Sharifi Z, Zeinali S Orphanet J Rare Dis. 2020; 15(1):14.

PMID: 31937337 PMC: 6961257. DOI: 10.1186/s13023-020-1296-x.

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