A rare form of limb girdle muscular dystrophy (type 2E) seen in an Iranian family detected by autozygosity mapping.
Sarcoglycanopathies (SGPs) constitute a subgroup of autosomal recessive limb girdle muscular dystrophies (LGMDs) which are caused by mutations in sarcoglycan (SGs) genes. SG proteins form a core complex consisting of α, β, γ and δ sarcoglycans which are encoded by SGCA, SGCB, SGCG and SGCD genes, respectively. Genetic defect, in any of these SG proteins, results in instability of the whole complex. This effect can be helpful in interpreting muscle biopsy results. Autozygosity mapping is a gene mapping approach which can be applied in large consanguineous families for tracking the defective gene in most autosomal recessive disorders. In the present study, we used autozygosity mapping, to find the gene responsible for muscular dystrophy. Proband was a 10-year-old boy referred to our center for ruling out DMD (Duchenne muscular dystrophy). According to the pedigree and clinical reports, we assessed him for SGPs. Haplotyping, using the four short tandem repeat (STR) markers for each of the SG genes, showed that the phenotype may segregate with SGCB gene; and observing two crossing overs which occurred within the gene suggested that the mutation might be in the first two exons of SGCB gene. Mutation analysis showed a 26 bp duplication (10 bp before the initiation codon till 13 bp after the ATG start codon). This will cause a frameshift in protein synthesis.
a Department of Molecular Medicine , Biotechnology Research Center, Pasteur Institute of Iran , Tehran , Iran ;|b Department of Medical Genetics , School of Medicine, Tehran University of Medical Sciences , Tehran , Iran ;
Marzieh
M
Mojbafan
c Pediatric Pathology Research Center, Mofid Children's Hospital, Shahid Beheshti Medical University [SBMU] , Tehran , Iran ;
Yalda
Y
Nilipour
d Pediatric Neurology Center of Excellence, Department of Pediatric Neurology , Mofid Children Hospital, Faculty of Medicine, ShahidBeheshti Medical university , Tehran , Iran ;
Seyed Hasan
SH
Tonekaboni
e Kawsar Human Genetics Research Center , Tehran , Iran.
Samira Dabbagh
SD
Bagheri
e Kawsar Human Genetics Research Center , Tehran , Iran.
Hamideh
H
Bagherian
e Kawsar Human Genetics Research Center , Tehran , Iran.
Zohreh
Z
Sharifi
e Kawsar Human Genetics Research Center , Tehran , Iran.
Zahra
Z
Zeinali
b Department of Medical Genetics , School of Medicine, Tehran University of Medical Sciences , Tehran , Iran ;
Javad
J
Tavakkoly-Bazzaz
a Department of Molecular Medicine , Biotechnology Research Center, Pasteur Institute of Iran , Tehran , Iran ;|e Kawsar Human Genetics Research Center , Tehran , Iran.
Sirous
S
Zeinali
D000328:Adult; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007492:Iran; D008297:Male; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D010375:Pedigree; D049031:Sarcoglycans / Q000235:genetics*
C483098:SGCB protein, human; D049031:Sarcoglycans
Autozygosity mapping; beta sarcoglycanopathy; limb girdle muscular dystrophy; mutation analysis