Homozygous Nonsense Mutation in the Sh3tc2 Gene Causing Charcot Marie Tooth Type Cmt4c

Background and aim: charcot-marie-tooth (cmt) disease is the most common hereditary peripheral neuropathy. cmt affected patients manifest symmetric, slowly progressive distal motor neuropathy of the arms and legs usually beginning in the first to third decade which is resulting in weakness and atrophy of the muscles in the feet and/or hands. the affected patients typically have distal muscle weakness and atrophy, weak ankle dorsiflexion, depressed tendon reflexes, and pes cavus foot deformity. genetically, cmt is a heterogeneous group of hereditary polyneuropathies. to date, more than 80 different genes are associated with cmt. this disease is classified to nine genetic subtypes cmt1, cmt2, cmt3, cmt4, cmt5, cmt6, cmtdi, cmtri and cmtx. cmt4 is an autosomal recessive demyelinating type. cmt4c, as one of the cmt4 subtypes, is caused by mutations in the sh3tc2 gene which is expressed in the nervous tissues, and localized to the plasma membrane and the perinuclear recycling compartment in schwann cells.methods: in this study, next generation illumina sequencing was used to enrich all exons of 280 genes involved in neuromuscular diseases in proband. to confirm the mutation found, sanger sequencing was performed.results: we have identified a novel homozygous nonsense mutation c2860t:p.r954x in the sh3tc2 gene. in addition, her parents were heterozygote for this mutation. carrier detection of other family members was performed, as well.conclusion: in general, this study uncovered a novel frame-shift insertion mutation in sh3tc2 gene in the family studied and such studies may help to conduct genetic counseling and prenatal diagnosis for individuals at the high risk of cmt.