DNA linkage analysis of 26 families with fragile X syndrome

Linkage data using the markers F9 (factor IX), DXS105 (cX55.7), DXS98 (4D-8), DXS52 (St14), DXS15 (DX13), and DXS134 (cpX67) are presented from 26 pedigrees segregating with fragile X (fra[X]) syndrome. Cytogenetic and DNA data were combined in 2-point linkage analysis for the estimation of lod scores and carrier probabilities in potential carriers. Recombination fractions (theta) corresponding to the maximum lod scores (Z) were obtained for F9 (Z = 2.78, theta = 0.15), DXS105 (Z = 1.72, theta = 14), DXS98 (Z = 3.74, theta = 0.00), DXS52 (Z = 3.53, theta = 0.17), DXS15 (Z = 4.03, theta = 0.11), and DXS134 (Z = 2.12, theta = 0.16) and for the fragile X locus (FRAXA). Recombination fractions between marker loci in the families are also presented. Discordance between the results of cytogenetic and DNA analyses in 2 potential carrier females was investigated by reexamination of the fragile site expression and was concluded to be due to the expression of the common fragile site at Xq27.2.