First Report of Two Novel Mutations in Alpha Sarcoglycan Gene in Two Iranian Families With Lgmd



Mojbafan M^{1, 2} ; Tonekaboni SH^{3, 4} ; Nilipour Y⁵ ; Tavakkolybazzaz J² ; Zeinali S^{1, 6}
Source: Genetics in the Third Millennium Published:2016

Abstract

The sarcoglycanopathies (SGPs) are a subgroup of autosomal recessive limb girdle muscular dystrophies (LG-MDs). 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 sarcoglycanopathies 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. two unrelated Iranian families, having 12affected patients, were investigated.Patient’screatine kinase level was high. IHC findings revealed muscular dystrophy suggestive of sarcoglycanopathy. 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 gene. Mutation analyses revealed novel homozygous deletions in two families; one of them was 11 base pairs in exon 4 and the other was a 2 nucleotide deletion in exon 6 deletions causeframeshift and premature stop codon. They result ineliminating 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. IHC studies combined with autozygosity mapping and mutation screening is an efficient diagnostic method in the sarcoglycanopathies. © 2016, Iranian Neurogenetics Society. All rights reserved.