Charcot-Marie-Tooth disease with intermediate motor nerve conduction velocities: Characterization of 14 C×32 mutations in 35 families
✍ Scribed by H Rouger; E LeGuern; N Birouk; R Gouider; S Tardieu; E Plassart; M Gugenheim; J-M Vallat; J-P Louboutin; P Bouche; Y Agid; A Brice
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 236 KB
- Volume
- 10
- Category
- Article
- ISSN
- 1059-7794
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✦ Synopsis
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.