Charcot–marie–tooth neuropathies: From clinical description to molecular genetics

Ninety‐five families with Charcot‐Marie‐Tooth (CMT) neuropathies were studied clinically, electrophysiologically (MNCVs and EMGs), and by molecular genetics. Fifty‐four families (56.8%) were type 1A mapped at 17p11.2‐p12 and DNA duplication was present in 50 (92.6% of CMT1A families). One family with type 1B (1.1%) mapped at 1q22‐q23 showed a point mutation of the myelin Po gene. Eighteen families (18.9%) were type CMT2 based on electrophysiological studies. Molecular genetics was not yet conclusive. Twenty CMT families were with X‐linked dominant inheritance ( CMTX1 ) (21.1%) mapped at Xq13.1 and connexin 32 (CX32) point mutations were present in 15 families (75%) (five nonsense mutations, eight missense mutations, two deletions). Two CMT families (2.1%) with X‐linked recessive inheritance showed no point mutations of CX32 and their mapping was different from CMTX1 , respectively at Xp22.2 for CMTX2 and at Xq26 for CMTX3 .© 1995 John Wiley &Sons, Inc.