CHARCOT-MARIE-TOOTH-DISEASE WITH INTERMEDIATE MOTOR-NERVE CONDUCTION VELOCITIES - CHARACTERIZATION OF 14 CX32 MUTATIONS IN 35 FAMILIES

Charcot-Marie-Tooth disease can be inherited either autosomal dominant ly or recessively or linked to the X chromosome. X-linked dominant Cha rcot Marie Tooth disease (CMTX) is a sensorimotor peripheral neuropath y in which males have usually more severe clinical symptoms and decrea sed nerve conduction velocities than do females. CMTX is usually assoc iated with mutations in exon 2 of the connexin 32 (Cx32) gene, DNA fro m 35 unrelated CMT patients, without the 17p11.2 duplication, but with median nerve conduction between 30 and 40 m/s, were tested for the pr esence of Cx32 mutations, The entire coding sequence of the Cx32 gene was explored using a rapid nonradioactive technique to detect single-s trand conformation polymorphisms (SSCP) on Large PCR fragments. Thirte en abnormal SSCP profiles were detected and characterized by sequencin g. In addition, systematic sequencing of the entire Cx32 coding region in the remaining index cases revealed another mutation that was not d etected by SSCP. A total of 14 mutations were found, five of which wer e not previously reported. These results demonstrate the high frequenc y (40%) of mutations in the coding region of the Cx32 gene in CMT pati ents with intermediate MNCV, without 17p11.2 duplications. Most of the se mutations (93%) can be detected by SSCP. (C) 1997 Wiley-Liss, Inc.