Linkage analyses between dominant X-linked Charcot-Marie-Tooth disease, and 15 Xq11-Xq21 microsatellites in a new large family: three new markers are closely linked to the gene

Abstract

X-linked dominant inheritance was suspected in a large family with Charcot-Marie-Tooth disease since no male to male transmission was observed, and since the sensory and motor neuropathy was more severe in males than in females. To test linkage to the dominant X-linked Charcot-Marie-Tooth disease (DCMTX) locus in Xq13, genotypes of 19 affected and 19 unaffected individuals from this family were determined for 4 microsatellite markers. Close linkage to mfd66 (DXS453) was found by bipoint analysis (Zmax = 4.8 at theta = 0.00). Multipoint analysis mapped the gene between the androgen receptor and DXYS1. In addition, linkage analysis performed with 11 microsatellite markers, derived from a high density map spanning 16 cM on Xq11-Xq21 revealed 3 new tightly linked loci: afm287zg1 (DXS1216), afm261zh5 and afm207zg5 (DXS995). Multipoint analysis localized the DCMTX gene to a 7.5 cM interval between afm123xd4 (DXS988) and afm116xg1 (DXS986). Combined analysis with these new microsatellites provides a powerful tool for carrier detection because of their high informativity and the small genetic distance (< 10 cM) between the markers flanking the gene.