Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32(GJB1) in Russian Charcot-Marie-Tooth neuropathy patients

Charcot-Marie-Tooth disease (CMT) and related inherited peripheral neuropat hies, including Dejerine-Sottas syndrome, congenital hypomyelination, and h ereditary neuropathy with liability to pressure palsies (HNPP), are caused by mutations in three myelin genes: PMP22, MPZ and Cx32 (GJB1). The most co mmon mutations are the 1.5 Mb CMTIA tandem duplication on chromosome 17p11. 2-p12 in CMT1 patients and the reciprocal 1.5 Mb deletion in HNPP patients. We performed a mutation screening in 174 unrelated CMT patients and three HNPP families of Russian origin. The unrelated CMT patients included 108 cl inically and electrophysiologically diagnosed CMT1 cases, 32 CMT2 cases, an d 34 cases with unspecified CMT, Fifty-nine CMT1A duplications were found, of which 58 belonged to the CMT1 patient group. We found twelve distinct mu tations in Cx32, six mutations in MPZ, and two mutations in PMP22. Of these respectively, eight, five, and two lead to a CMT1 phenotype. Eight mutatio ns (Cx32: Ile20Asn/ Gly21Ser, Met34Lys, Leu90Val, and Phe193Leu; MPZ: Asp13 4Gly, Lys138Asn, and Thr139Asn; PMP22: ValSer25-26del) were not reported pr eviously. Phenotype-genotype correlations were based on nerve conduction ve locity studies and mutation type, Hum Mutat 15:340-347, 2000. (C) 2000 Wile y-Liss, Inc.