Study Of A Family With A Novel Mutation Of Gap Junction Protein β1(GJB1) Gene In X-linked Charcot-Marie-Tooth Disease

[Background and Objective]X-linked dominant Charcot-Marie-Tooth disease (CMTX) is an inherited neuropathy caused by mutations affecting the gap junction protein beta 1 (GJB1) gene coding for 283 amino, which is located within the Xq13 region. Over 300 different mutations in the GJB1 gene have been identified, which found in all regions of GJB1 genes.Males are usually more severely affected and the onset of a motor deficit is earlier than in females. In the pedigree, the affliction is never transmitted from father to son. Motor nerve conduction velocity (NCV) is light to moderateslow, but in some female patients may be near-normal. Although much is being learned about the genetic basis of CMTX, several basic questions remain unanswered. There is continuing controversy as to whether CMTX is primarily a demyelinative or axonal-loss neuropathy. Notably, the electrophysiological characteristics of CMTX have not been defined completely. In view of these uncertainties, we report a Chinese CMTX family with a novel mutation in GJB1 gene. This article will study the clinical characteristics and genetic mechanism of this family, and looking forward to discover a new genes or new mutations.[Method]We studied a four-generation family and 7 patients affected. All patients were consistent with the second meeting of the CMT European Union diagnostic criteria established in 1998. CMTX 20 members in the family were studied clinically, and 3 patients were studied electrophysiologically. Sural nerve biopsy was performed in the proband and his mother. And mutation analysis of GJB1 gene was performed of the 20 members.[Result]Except 2 asymptomatic carriers, all patients presented muscle wasting and a predominating weakness of distal parts of the lower limbs, and mild to moderate sensory impairments. Patients of males are more severe than females in clinically. Elctrophysiological examinations, motor nerve conduction velocity (MNCV) of the median nerve was light to moderate slow, and motor nerve conduction block and dispersion was found, and sensory nerve conduction amplitude significantly decreased or disappeared。Sural nerve biopsy of the proband and his mother confirmed a predominantly demyelinating neuropathy. Asn2Lys was found in this family, but not in 11 normal person in this family and 25 normal controls out of the family, which suggests Asn2Lys is the pathogenic mutation in this family.[Conclusion]The results are consistent with the diagnosis of CMTX. This family represents a novel mutations GJB1 gene in CMTX. The elctrophysiological examinations of motor nerve conduction block and dispersion are special features of CMTX, Which may be associated with the mutation.