LINKAGE ANALYSES BETWEEN DOMINANT X-LINKED CHARCOT-MARIE-TOOTH-DISEASE, AND 15 XQ11-XQ21 MICROSATELLITES IN A NEW LARGE FAMILY - 3 NEW MARKERS ARE CLOSELY LINKED TO THE GENE

X-linked dominant inheritance was suspected inheritance was suspected in a large family with Charcot-Marie-Tooth disease since no male to ma le transmission was observed, and since the sensory and motor neuropat hy was more sever in males than in females. To test linkage to the dom inant X-linked Charcot-Marie-Tooth disease (DCMTX) locus in Xq13, geno types of 19 affected and 19 unaffected individuals from this family we re determined for 4 microsatellite markers. Close linkage to mfd66 (DX S453) was found by bipoint analysis (Zmax = 4.8 at theta = 0.00). Mult ipoint analysis mapped the gene between the androgen receptor and DXYS 1. In addition, linkage analysis performed with 11 microsatellite mark ers, derived from a high density map spanning 16 cM on Xq11-Xq21 revea led 3 new tightly linked loci: afm287zg1 (DXS1216), afm261zh5 and afm2 07zg5 (DXS995). Multipoint analysis localized the DCMTX gene to a 7.5 cM interval between afm123xd4 (DXS988) and afm116xg1 (DXS986). Combine d analysis with these new microsatellites provides a powerful tool for carrier detection because of their high informativity and the small g enetic distance (< 10 cM) between the markers flanking the gene.