A rare form of limb girdle muscular dystrophy (type 2E) seen in an Iranian family detected by autozygosity mapping

Abstract

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.

Reporting a rare form of myopathy, myopathy with extrapyramidal signs, in an Iranian family using next generation sequencing: a case report

“…Autozygosity mapping is a good and practical approach in the gene tracking of heterogeneous disorders in consanguineous families [12,13]. Since the cost of next generation sequencing continues to decreasethe NGS will be widly used in identifying pathogenic variants [14].…”

Patterns of Clinical Progression Among Patients With Autosomal Recessive Limb-Girdle Muscular Dystrophy: A Systematic Review

“…1, see Table , Supplemental Digital Content A.2 , http://links.lww.com/JCND/A58). 12–142 Included data were primarily derived from case reports (n = 74), although patient-level data were also commonly available from retrospective (n = 22) and prospective (n = 18) studies. Of studies reporting a geographic location, over 35 countries were represented, with the most studies conducted in the United States (n = 14) and Germany (n = 13).…”

Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis

“…In addition, translational profiling of astrocytes from hSOD1 G37R mice identified upregulation of inflammatory genes and down-regulation of metabolic genes belonging to the pathways controlled by the liver X receptor and the peroxisome proliferator activated receptor [60]. Meanwhile, a transcriptome analysis of astrocytes isolated from hSOD1 G93A mice revealed early gene expression changes linked to ion homeostasis [61]. Therefore, significant changes in the biology of astrocytes accompany motor neuron degeneration in ALS-models, supporting the idea that astrocytes play an active role in mutant hSOD1-mediated toxicity.…”