First Iranian Family with a Novel Missense Variant in Gene Causing Charcot-Marie-Tooth Disease.

A heterogeneous clinical and genetic Charcot-Marie-Tooth (CMT) disease, with peripheral nerve damage resulting in chronic motor and sensory polyneuropathy, has been linked to the mutation in over a hundred genes. We report the adult onset of CMT in three siblings of an Iranian family manifesting with muscle weakness and wasting, foot drop, and pes cavus. Whole-exome sequencing (WES) identified a novel homozygous missense mutation in the gene, inherited from obligatory carrier parents. This likely pathogenic variant contributes to chronic demyelinating sensorimotor polyneuropathy and conduction blocking in the ulnar and median nerves in these patients. To our knowledge, our study is the first report on MYO9B-related CMT in Iranian patients. Previously, a few variations in the gene were reported to cause CMT. Here we emphasize the potential disruptive role of the detected variant of in CMT pathogenesis and also highlight the importance of WES for the proper diagnosis of CMT disease. We also compared the clinical presentations of Iranian and Italian patients expanding the clinical and mutational spectrum of MYO9B-related neuropathies.