EVIDENCE FOR A RECESSIVE PMP22 POINT MUTATION IN CHARCOT-MARIE-TOOTH DISEASE TYPE-1A

Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant n europathy that can be caused by dominant point mutations in PMP22 whic h encodes a peripheral nerve myelin protein. Usually, CMT1A is caused by the duplication of a 1.5-megabase (Mb) region on chromosome 17p11.2 -p12 containing PMP22. Deletion of a similar 1.5-Mb region is associat ed with hereditary neuropathy with liability to pressure palsies (HNPP ), a clinically distinct neuropathy. We have identified a severely aff ected CMT1 patient who is a compound heterozygote for a recessive PMP2 2 point mutation, and a 1.5 Mb deletion in 17p11.2-p12. A son heterozy gous for the PMP22 point mutation had no signs of neuropathy, while tw o others heterozygous for the deletion had HNPP, suggesting that point mutations in PMP22 can result in dominant and recessive alleles contr ibuting to CMT1A.