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Charcot‐Marie‐Tooth disease with intermediate motor nerve conduction velocities: Characterization of 14 C×32 mutations in 35 families
Author(s) -
Rouger H,
LeGuern E,
Birouk N,
Gouider R,
Tardieu S,
Plassart E,
Gugenheim M,
Vallat JM,
Louboutin JP,
Bouche P,
Agid Y,
Brice A
Publication year - 1997
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(1997)10:6<443::aid-humu5>3.0.co;2-e
Subject(s) - biology , single strand conformation polymorphism , genetics , tooth disease , coding region , exon , mutation , gene , gene duplication , connexin 32 , microbiology and biotechnology , connexin , intracellular , gap junction
Charcot‐Marie‐Tooth disease can be inherited either autosomal dominantly or recessively or linked to the X chromosome. X‐linked dominant Charcot‐Marie‐Tooth disease (CMTX) is a sensorimotor peripheral neuropathy in which males have usually more severe clinical symptoms and decreased nerve conduction velocities than do females. CMTX is usually associated with mutations in exon 2 of the connexin 32 (C×32) gene. DNA from 35 unrelated CMT patients, without the 17p11.2 duplication, but with median nerve conduction between 30 and 40 m/s, were tested for the presence of C×32 mutations. The entire coding sequence of the C×32 gene was explored using a rapid nonradioactive technique to detect single‐strand conformation polymorphisms (SSCP) on large PCR fragments. Thirteen abnormal SSCP profiles were detected and characterized by sequencing. In addition, systematic sequencing of the entire C×32 coding region in the remaining index cases revealed another mutation that was not detected by SSCP. A total of 14 mutations were found, five of which were not previously reported. These results demonstrate the high frequency (40%) of mutations in the coding region of the C×32 gene in CMT patients with intermediate MNCV, without 17p11.2 duplications. Most of these mutations (93%) can be detected by SSCP. Hum Mutat 10:443–450, 1997. © 1997 Wiley‐Liss, Inc.