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Screening for mutations in the peripheral myelin genes PMP22 , MPZ and Cx32 ( GJB1 ) in Russian Charcot‐Marie‐Tooth neuropathy patients
Author(s) -
Mersiyanova Irina V.,
Ismailov Sookhrat M.,
Polyakov Alexandr V.,
Dadali Elena L.,
Fedotov Valeriy P.,
Nelis Eva,
Löfgren Ann,
Timmerman Vincent,
Van Broeckhoven Christine,
Evgrafov Oleg V.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(200004)15:4<340::aid-humu6>3.0.co;2-y
Subject(s) - peripheral myelin protein 22 , hum , gene duplication , mutation , genetics , biology , phenotype , myelin , genotype , point mutation , peripheral neuropathy , pathology , gene , medicine , endocrinology , central nervous system , art , performance art , art history , diabetes mellitus
Charcot‐Marie‐Tooth disease (CMT) and related inherited peripheral neuropathies, including Dejerine‐Sottas syndrome, congenital hypomyelination, and hereditary neuropathy with liability to pressure palsies (HNPP), are caused by mutations in three myelin genes: PMP22, MPZ and Cx32 ( GJB1 ). The most common mutations are the 1.5 Mb CMT1A 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 clinically and electrophysiologically diagnosed CMT1 cases, 32 CMT2 cases, and 34 cases with unspecified CMT. Fifty‐nine CMT1A duplications were found, of which 58 belonged to the CMT1 patient group. We found twelve distinct mutations in Cx32 , six mutations in MPZ, and two mutations in PMP22. Of these respectively, eight, five, and two lead to a CMT1 phenotype. Eight mutations ( Cx32 : Ile20Asn/Gly21Ser, Met34Lys, Leu90Val, and Phe193Leu; MPZ : Asp134Gly, Lys138Asn, and Thr139Asn; PMP22 : ValSer25‐26del) were not reported previously. Phenotype–genotype correlations were based on nerve conduction velocity studies and mutation type. Hum Mutat 15:340–347, 2000. © 2000 Wiley‐Liss, Inc.