A Novel Mutation 605 (T＞A) In CX32 Gene Causes X-linked Recessive Charcot-Marie-Tooth Disease

Background: Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with a prevalence of 1 in 2 500. Distal muscle weakness and atrophy, sensory loss and reduced or absent tendon reflexes, pescavus, hammer toes, steppage gait are among the main symptoms. There are several modes of inheritance: autosomal dominant (AD), autosomal recessive (AR), X-linked dominant (XD) and X-linked recessive (XR). CMT is subdivided into two main types based on neurophysiologic and neuropathologic studies: CMT1, the demyelinating form, exhibits moderately to severely reduced motornerve conduction velocities (the median nerves MCV<38 m/s), and onion bulb formation on the nervebiopsy, and CMT2, the axonal form, shows normal or mildly reduced MNCVs (the median nerves MCV> 38 m/s), and axon loss on the nerve biopsies. Up to now there is no really effective treatment for this disease, therefore it is important to provide an accurate genetic diagnosis and prenatal diagnosis to the CMT family.Objective: To identify the disease causing gene mutation, unveal the underlied pathogenesis and provide informative genetic counseling in a Chinese family with X-linked recessive CMT.Methods: Polymerase chain reaction (PCR) and sequencing were applied to detect the mutation in CX32 gene in a Chinese CMT family. Denaturing high performance liquid chromatography (DHPLC) analysis was performed to screen CX32 gene for the unknown variations in 120 normal Chinese males. To examine the effect of the mutation on CX32 protein, we employed Hela cells expressing Cx32/EGFP as a model system.Results: A novel mutation 605 (T>A) was detected in the CX32 gene of all four affected members in the family which was not found in the 120 normal males. By using fluorescent microscope, We observed the gap junction plaques in the wild type Cx32/EGFP Hela cells but not in the mutated ones.Conclusion:1. The mutation in CX32 gene causes the CMT disease in the family.2. The novel mutation 605(T>A) in CX32 gene can cause X-linked recessive Charcot-Marie-Tooth disease.3. The mutation 605 (T>A) may decrease the formation of the gap junction plaques on the cell membrane, wich underlie the pathogenesis of CMT disease.