X-linked mental retardation: Evidence for a recent mutation in a five-generation family (MRX65) linked to the pericentromeric region

We report linkage analysis in a new family with nonspecific X-linked mental retardation, using 27 polymorphic markers covering the entire X-chromosome , We could assign the underlying disease gene, denoted MRX65, to the perice ntromeric region, with flanking markers DXS573 in Xp11.3 and DXS990 in Xq21 .33. A maximum LOD score of 3.64 was found at markers ALAS2 (Xp11.22) and D XS453 (Xq12) at theta = 0. Twenty-five of the 58 reported MRX families are linked to a region that is partially overlapping with the region reported h ere, Extension of the pedigree showed a number of unaffected distant relati ves with haplotypes corresponding to the disease locus. Apparently, a new m utation in a female is causative for the disease in the family reported her e. Furthermore, we show the importance of combining clinical, cytogenetic, and molecular studies since one of the family members, expected to be affec ted by the same genetic defect, has a 48,XXXY karyotype. Am. J. Med. Genet. 85:305-308, 1999 (C) 1999 Wiley-Liss, Inc.