A novel mutation in alpha sarcoglycan gene in an Iranian family with limb girdle muscular dystrophy 2D.
OBJECTIVE
The sarcoglycanopathies (SGPs) are a subgroup of autosomal recessive limb girdle muscular dystrophies. They are caused by mutations in gamma, alpha, beta, and delta sarcoglycans (SGs) genes. Alpha-SGPs are the most frequent form of SGPs. Muscle biopsy studies in patients with SGPs have indicated that loss of one SG subunit leads to instability of whole SG complex. Autozygosity mapping is a powerful gene mapping approach for rare recessive inherited disorders in consanguineous families.


METHODS
In the present study, proband was a 9 year old girl from consanguineous parents. She was diagnosed at the age of 5 when she had problems climbing stairs. Her creatine kinase level was 16428 U/L. Proximal weakness and ankle contracture were also observed in the patient.


METHODS
Autozygosity mapping, using short tandem repeat (STR) markers linked to the SG genes, showed co-segregation of the phenotype with STR markers linked to the SGCA (Alpha-sarcoglycan) gene. Her muscle biopsy also suggested alpha sarcoglycanopathy. Mutation analyses revealed a novel homozygous deletion of 11 base pairs in exon 4 of this gene. This deletion introduces a premature termination codon after the 4th amino acid. This will eliminate the expression of the downstream part of the extracellular domain of the protein. This domain has a critical role by associating with other molecules of dystrophin-glycoprotein complexes.


CONCLUSIONS
IHC (Immunohistochemistry) studies combined with autozygosity mapping and mutation screening is an efficient diagnostic method in the SGPs.
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, ShahidBeheshti Medical University [SBMU] , Tehran , Iran.
Yalda
Y
Nilipour
d Pediatric Neurology Research Center , ShahidBeheshti University of Medical Sciences , Tehran , Iran.|e Pediatric Neurology Center of Excellence, Department of Pediatric Neurology, Mofid Children Hospital, Faculty of Medicine , ShahidBeheshti Medical University , Tehran , Iran.
Seyed Hasan
SH
Tonekaboni
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.|f Kawsar Human Genetics Research Center , Tehran , Iran.
Sirous
S
Zeinali
D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D007492:Iran; D009154:Mutation / Q000235:genetics*; D058088:Sarcoglycanopathies / Q000235:genetics*; D049031:Sarcoglycans / Q000235:genetics*
D049031:Sarcoglycans
Alpha-sarcoglycan; Autozygosity mapping; Immunohistochemistry; Limb girdle muscular dystrophy; Sarcoglycanopathy