Mutation of Cx32 gene,clinical and electrophysiological features in patients with Charcot-Marie-Tooth disease / 临床神经病学杂志

ABSTRACT

Objective To investigate the mutation of Cx32 gene,clinical and electrophysiological features of Chinese patients with Charcot-Marie-Tooth(CMT) disease.Methods 24 CMT probands were selected for Cx32 mutation screening after the exclusion of the CMT1A 1.5 Mb duplication and male-to-male transmission.The motor and sensory nerve conduction studies were performed in all probands and most of their affected family members to establish the clinical CMT1,CMT2 or CMT intermediate diagnosis.The presence of mutations in the coding region of Cx32 was detected by single-strand conformation polymorphism analysis combined with direct sequencing.Results It was found 7 different point mutations in the coding region of Cx32 in 1 sporadic CMT1 patient and 6 X-linked inherited families,including 4 families with CMT1 diagnosis and 2 families with CMT intermediate diagnosis.There were 20 male CMTX patients,6 female CMTX patients and 12 asymptomatic female carriers among 38 family members bearing Cx32 mutation.All of the 26 patients were mildly to moderately affected clinically.Conclusions Seven different Cx32 point mutations were detected and the percentage of Chinese CMT families with Cx32 mutation is about 10% in our study.The inheritance model of CMT secondary to Cx32 mutation could be X-linked dominant,X-linked recessive or sporadic.Male patients are usually more severly affected than females with slower nerve conduction velocities.Cx32 mutation screening should be firstly performed in those CMT families without male-to-male transmission and CMT1A duplication.