Linkage between the fragile X and F9, DXS52 (St14), DXS98 (4D-8) and DXS105 (cX55.7)

Linkage data using the markers F9, DXS105 (cX55.7), DXS98 (4D-8) and DXS52 (St14) are presented from 22 kindreds segregating with the fragile X. Two-point linkage analysis was carried out taking into account cytogenetic results and penetrance classes defined by mental impairment status of mothers. Recombination frequencies (theta) corresponding to the maximum z scores (z) were obtained between F9 (z = 3.48, theta = 0.18), DXS105 (z = 5.06, theta = 0.07), DXS98 (z = 4.79, theta = 0.01) and DXS52 (z = 6.44, theta = 0.09) and the fragile X. Recombination frequencies between marker loci in fragile X families are also presented. These recombination frequencies need to be combined with those from other studies in order to determine the best estimates of map distances for use in genetic counselling, until markers closer to the fragile X, or at the fragile X, can be used. Most potential fra(X) heterozygotes were informative for flanking markers using the above 4 probes. Carrier risks were determined by 3-point analysis using informative flanking markers, taking into account cytogenetic results. Low level fra(X) expression occurred in 2 probable non-carriers; emphasising the need for extreme caution in the interpretation of low rates of expression.