Linkage and genetic counselling for the fragile X using DNA probes 52A, F9, DX13, and ST14

Linkage data using the markers DXS51, F9, DXS15, and DXS52 are presented from 14 pedigrees segregating with the fragile X. Cytogenetic and DNA data were combined by two- or three-point linkage analysis for estimation of lod scores and carrier probabilities in potential carriers. Recombination frequencies (θ) corresponding to maximum z scores (z) were obtained for DXS51 (z = 3.45, θ = 0.0), DXS15 (z = 0.40, θ = 0.06), F9 (z = 3.15, θ = 0.09), and DXS52 (z = 3.60, θ = 0.11) with the fragile X. Considerable alterations to carrier probabilities occurred in some cases, especially when flanking markers were informative. The chance of mentally impaired offspring was reduced to 1% for five of eight women with prior carrier probabilities of 32%. Three pedigrees were identified in which mutation had possibly occurred. An alternative explanation for two of these was inheritance of the fragile X from normal males and for the other inheritance from a clinically normal woman. Probabilities were computed for each of these alternatives.