LINKAGE ANALYSIS IN 3 FAMILIES WITH NONSPECIFIC X-LINKED MENTAL-RETARDATION

Nonspecific X-linked mental retardation (XLMR) is a common disorder. T he number of genes involved in this condition is not known, but it is estimated to be more than 10. We present a clinical and linkage study on 3 families with XLMR, All families were analyzed using highly polym orphic markers covering the X chromosome; screening for the fragile X mutation was negative, The first family (MRX 36) consisted of 1 female and 4 male patients in 3 generations and 7 healthy individuals. Consi dering the female as an expressing heterozygous carrier, a maximum LOD score of 3.41 was reached in region Xp21.2-Xp22.1. Considering her ph enotype to be unknown, a LOD(max) of 1.97 was reached in the same regi on. The second family consisted of 5 affected and 6 healthy males with mild to borderline mental retardation. Linkage analysis using an X-li nked recessive model with full penetrance and no phenocopies excluded linkage over almost the entire X chromosome, Using alternative models, including an affecteds-only analysis, a LOD(max) of 1.49 was found in region Xq24-28. The third family, consisting of 4 male patients with moderate mental retardation in 1 generation yielded a LOD(max) of 0.9 in region Xp22.13-11.3. However, even in this small pedigree, exclusio n mapping was able to exclude very large parts of the X chromosome and in this way identify a likely candidate region. (C) 1996 Wiley-Liss, Inc.