Multipoint linkage analysis in Menkes disease.

Abstract Linkage analyses were performed in 11 families with X-linked Menkes disease. In each family more than one affected patient had been diagnosed. Forty informative meioses were tested using 11 polymorphic DNA markers. From two-point linkage analyses high lod scores are seen for DXS146 (pTAK-8; maximal lod score 3.16 at recombination fraction [theta] = .0), for DXS1 (p-8; maximal lod score 3.44 at theta = .0), for PGK1 (maximal lod score 2.48 at theta = .0), and for DXS3 (p19-2; maximal lod score 2.90 at theta = .0). This indicates linkage to the pericentromeric region. Multilocus linkage analyses of the same data revealed a peak for the location score between DXS146(pTAK-8) and DXYS1X(pDP34). The most likely location is between DXS159 (cpX289) and DXYS1X(pDP34). Odds for this location relative to the second-best-supported region, between DXS146(pTAK-8) and DXS159 (cpX289), are better than 74:1. Visualization of individual recombinant X chromosomes in two of the Menkes families showed the Menkes locus to be situated between DXS159(cpX289) and DXS94(pXG-12). Combination of the present results with the reported absence of Menkes symptoms in male patients with deletions in Xq21 leads to the conclusion that the Menkes locus is proximal to DXSY1X(pDP34) and located in the region Xq12 to Xq13.3.