Charcot-Marie-Tooth (CMT) is a heterogeneous group of progressive disorders, characterized by chronic motor and sensory polyneuropathy. This hereditary disorder is related to numerous genes and varying inheritance patterns. Thus, many patients do not reach a final genetic diagnosis. We describe a 13 years old girl presenting with sub-acute progressive bilateral leg weakness and gait instability. Extensive laboratory studies and Magnetic Resonance Imaging scan of the spine were normal. Nerve conduction studies revealed severe lower limb peripheral neuropathy with prominent demyelinative component. Following presumptive diagnosis of chronic inflammatory demyelinating polyneuropathy, the patient received repeated treatment with steroids and intravenous immunoglobulins with no apparent improvement. Whole exome sequencing revealed a novel heterozygous c.2209C>T (p.Arg737Trp) mutation in the MARSgene (OMIM 156560). This gene has recently been related to CMT type 2U. In-silico prediction programs classified this mutation as a probable cause for protein malfunction Family segregation analysis study revealed that the patient had inherited the variant from her 60-years old mother, reported as healthy. Neurologic examination of the mother demonstrated decreased limb reflexes, with nerve conduction studies consistent with demyelinative and axonal sensory-motor polyneuropathy. Our report highlights the importance of next generation sequencing approach to facilitate the proper molecular diagnosis. This approach might prevent unnecessary diagnostic testing and potentially harmful medical treatment.
