PERICENTROMERIC GENES FOR NONSPECIFIC X-LINKED MENTAL-RETARDATION (MRX)

Extensive linkage analyses in three families with non-specific X-linke d mental retardation (MRX) have localized the gene in each family to t he pericentromeric region of the chromosome. The MRX17 gene is localiz ed with a peak lod of 2.41 (theta = 0.0) with the trinucleotide repeat polymorphism at the androgen receptor (AR) gene locus. This gene lies in the interval between the markers DXS255 and DXS990, as defined by recombinants. The MRX18 gene maps to the interval between the markers DXS538 and DXS1126, with a peak lod score of 2.01 (theta = 0.0) at the PFC gene locus. In the third family (Family E) with insufficient info rmative meioses for assignment of an MRX acronym, the maximum lod scor e is 1.8 at a recombination fraction of zero for several marker loci b etween DXS207 and DXS426. Exclusions from the regions of marker loci s panning Xq support the localization of the MRX gene in Family E to the pericentromeric region. Localizations of these and other MRX genes ha ve determined that MRX2 and MRX19 map to distal Xp, MRX3, and MRX6 map to distal Xq, whilst the majority cluster in the pericentromeric regi on. In addition, we confirm that there are at least two distinct MRX g enes near the centromere as delineated by the non-overlapping regional localizations of MRX17 and MRX18. Determination of these non-overlapp ing localizations is currently the only means of classifying non-syndr omal forms of mental retardation and determining the minimum number of MRX loci. (C) 1994 Wiley-Liss, Inc.