Refined 2.7 centimorgan locus in Xp21.3-22.1 for a nonspecific X-linked mental retardation gene (MRX54)

Nonspecific X-linked mental retardation (MRX) is a heterogeneous condition in which mental retardation (MR) appears to be the only consistent manifest ation. A large genetic interval of assignment obtained on individual famili es by linkage analysis, genetic, heterogeneity, and phenotypic variability usually are major obstacles to fine- map and identify the related disease g enes. Here we report on a large Tunisian family (MRX54) with an MRX conditi on. X-linked recessive inheritance is strongly suggested by the segregation of MR through seven unaffected carrier females to 14 affected males in two generations. Two-point linkage analysis demonstrated significant linkage b etween the disorder and several markers in Xp21.3-22.1 (maximum LOD score Z (max) = 3.56, recombination fraction 0 = 0 at DXSf202), which was confirmed by multipoint linkage analyses. Recombinant events observed with the flank ing markers DXS989 and DXS1218 delineate a refined locus of approximately 2 .7 cM in accordance with the physical distance between these two markers. T he small interval of assignment observed in this family overlaps not only w ith nine large MRX loci previously reported in Xp21.3-22.1 but also with tw o inherited microdeletions in Xp21.3-22.1 involved in non-specific MR, Alth ough the involvement of several genes located in the Xp21.3-22.1 region can not be ruled out, data reported in this study could be used as a starting p oint for the search of such gene(s), Am. J. Med. Genet. 85:276-282, 1999. ( C) 1999 Wiley-Liss, Inc.