LINKAGE AND MUTATION ANALYSIS OF CHARCOT-MARIE-TOOTH NEUROPATHY TYPE-2 FAMILIES WITH CHROMOSOMES 1P35-P36 AND XQ13

A locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT 2A) was assigned by linkage analysis to chromosome 1p35-p36. We examin ed 11 unrelated CMT2 families for linkage to CMT2A using short tandem repeat (STR) polymorphisms. Only one family showed suggestive evidence for linkage to 1p35-p36. Further, because of an overlap in electrophy siologic data between CMT2 and CMTX female patients, we screened 6 of 11 CMT2 families compatible with dominant X-linkage for mutations in t he connexin 32 (Cx32) gene at Xq13. There was a Cx32 mutation in one f amily, whereas another family showed suggestive evidence for Xq13 link age upon analysis with STR polymorphisms. Our results suggest that the CMT2A locus is a minor locus for CMT2, additional linkage studies are needed to localize other CMT2 loci, and Cx32 mutations may be the und erlying genetic defect in some CMT2 families.