A Novel Connexin32Mutations Cause X-linked Recessive Charcot-maire-Tooth Disease

Objective: In this study we analysis the mutation in the gap junction protein beta1(Connexin32) gene of a Chinese X-linked Charcot-Marie-Tooth disease (CMTX) family andclinical symptom,electrophysiological characteristics as well.Materials and Methods: The proband who was diagnosed as Charcot-Marie-Toothdisease by Neurology Department of the first Bethune Hospital of Jilin University and hisfamily members the were studied by clinical examination and CX32gene mutation analysisby pcr and sequencing. The proband was studied electrophysiologically.Results: This family have no male to male transmission in pedigrees conforming toX-linked resessive hereditary. Four generations family contains fourteen male and fourteenfemale members and have five patients who are all male. Age of onset was14to30years.The duration was1.5to28years.The initial symptoms was wrestling constantlywhen running and jumping. Five male patients have the typical CMT phenotype: atrophy andweakness in the distal muscles of the lower limbs,absent tendon reflexes and vibrationsensory impairment. Five female family members don’t have any complains except mildvibration sensory impairment of lower limbs. Two male children of the fourth generationcan’t be diagnosed because of mild symptoms and lacking electrophysiological examinations.Electrophysiological examinations of proband confirmed both demyelinating and axonlneuropathy. five male patients and two children were all found c.110T-C(Val37Ala)mutation but not in20normal controls. Five female family members have heterozygousmutation in CX32who are carriers.Conclusion: This is a X-linked resessive CMT family representing a novelc.110T-C(Val37Ala) mutation in the CX32,suggesting that a novel c.110T-C(Val37Ala)mutation in the CX32can cause X-linked resessive CMT disease.This site is conserved indifferent species,but the mutation rate in large papulation should be studied further.