A novel frameshift insertion 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 and resulting in weakness and atrophy of the muscles in the feet and/or hands. The affected individual typically has distal muscle weakness and atrophy, weak ankle dorsiflexion, depressed tendon reflexes, and pes cavus foot deformity. CMT is a heterogeneous group of hereditary polyneuropathies. To date, more than 80 different genes are associated with CMT. CMT disease is classified into nine genetic subtypes (CMT1, CMT2, CMT3, CMT4, CMT5, CMT6, CMTDI, CMTRI and CMTX).Methods : Molecular genetic testing approaches can include gene-targeted testing (single-gene testing and multi-genes panel) and comprehensive genomic testing (whole exome sequencing, exome array). In this study, Next Generation Illumina Sequencing was used to enrich all exons of more than 22000 genes as well as some other important genomic regions in proband. Subsequently, Sanger sequencing was used for confirmation of mutation found.Results : The results showed a novel homozygous frame-shift insertion mutation 3472dupG:p.V1158fs in the SH3TC2 gene of proband. In addition, her parents were heterozygote for this mutation. Carrier detection of other family members was performed, as wellConclusion : In general, this study uncovered one rare 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.

Keywords:

Charcot Marie Tooth (CMT) , SH3TC2 , frame-shift insertion mutation , genetic counseling