Charcot -- Marie -- Tooth neuropathy type 1A with both duplication and non-duplication

We studied a family with nine of twenty members affected withCharcot — Marie — Tooth disease type 1A (CMT1A).The proband and her four affected sibs showed no duplicationof the 17p11.2–p12 (CMT region). Two of the proband'saffected daughters and three affected grandchildren showed duplicationof the PMP-22 gene and of the marker VAW409R3 but not of themarkers VAW412R3 and EW401. Pulsed field gel electrophoresis(PFGE) revealed a 220 kb SacII fragment in one CMT1A patientwith duplication instead of a 500 kb SacII fragment as previouslyreported (1, 3, 4, 6–9). Our findings suggest a smallersize of the duplication in this CMT1A family. The disease segregateswith the same haplotype in both duplicated and nonduplicatedCMT1A patients. The clinical phenotype showed more severe weaknesswith earlier onset and motor nerve conduction velocities werecharacterized by more significant slowing in the patients withduplication than in the patients who did not show duplication.