Maryam Tahmasebi Birgani - Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Mohammadreza Hajjari - Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Neda Golchin - Noor Genetics Lab. Ahvaz, Iran
Bita Shalbafan - Iranian Social Security Organization, Labafinejad Hospital, Tehran, Iran

Objective(s): Charcot-Marie Tooth disease (CMT) is one of the main inherited causes of motor and sensory neuropathies with variable expressivity and age-of onset. Although more than 70 genes have been identified for CMT, more studies are needed to discover other genes involved in CMT. Introduction of whole exome sequencing (WES) to capture all the exons may help to find these genes.Materials and Methods: Here, we tried to find the genetic cause of the neuropathy in two Iranian brothers using WES. Blood sample was collected from probands and their family members to extract the genomic DNA. The extracted DNA from one of the affected case was subjected for WES. The variant calls were filtered  to reveal the pathogenic variant. Presence of the candidate mutation was confirmed using Sanger sequencing. The pathogenic potential of the variant was examined using in silico software. Using ClustalW multiple alignment, the presence of variant in conserved domain of protein was investigated. The parent and another affected boy were also checked for presence of the variant using PCR-sequencing. Results: The obtained data presented a novel TTC del mutation in CDS 738 of dystrophin related protein 2 (DRP2) gene, which was validated by sequencing. The variant was located in a conserved domain of DRP2 protein and predicted as pathogenic. Two affected boys were hemizygous for the mutation and received the mutation from mother. Conclusion: Here, we provided the evidence for the contribution of DRP2 in CMT. Also, the symptoms shed light on molecular aspect of this genetically heterogeneous disease.

Charcot-marie tooth disease, Dystrophin-related protein 2 gene (DRP2), Genetic heterogeneity, Hereditary sensory and Motor neuropathy, Whole exome sequencing