Exome sequencing identifies a novel pathogenic CLCN1 mutation in an Iranian family with Myotonia Congenita: A case report

Background Myotonia congenita (MC) is a non-dystrophic genetic disorder caused by mutations in the chloride channel gene in the skeletal muscle (CLCN1). Muscle stiffness, weakness, and delayed skeletal relaxation are all characteristics of this genetic disorder. Materials and methods We sequenced the entire coding region and exon-intron boundaries of the CLCN1 gene in an Iranian pedigree using whole-exome sequencing (WES). A co-segregation analysis was also performed in the proband and both parents using Sanger sequencing . Moreover, bioinformatics analyses were carried out to predict mutation's possible function and pathogenicity. Results In exon 17 of the CLCN1 gene, a novel deleterious homozygous mutation c.2116G > T; p. E706Ter was identified. An in silico analysis identified this mutation as a potential pathogenic variant. The level of mutant transcripts appears to decrease due to nonsense-mediated decay. The mutation likely resulted in a considerably shortened protein that lacked conserved and functional domains such as CBS2. Conclusions We surveyed the clinical and genetic characteristics of an Iranian family with MC and recognized a novel pathogenic variant c.2116G > T; p. E706Ter in the CLCN1 gene. This variant is a nonsense mutation , probably leading to a premature stop codon . Our findings could aid in the improvement of gene mutation databases and the identification of the causes of MC.