Evidence for a new X-linked mental retardation gene in Xp21-Xp22: Clinicaland molecular data in one family

Linkage analysis was performed in three generations of a French family segr egating a syndromal form of X-linked mental retardation, All affected males had neonatal hypotonia, seizures, muscular hypodevelopment, and severe men tal deficiency. A peak lod score of 2.90 at a recombination fraction of the ta = 0 was detected for DXS 1052 and DXS 451 (Xp22.13). Recombination betwe en the disease locus and the polymorphic markers in DXS7163 and DXS1238 sug gested a gene mapping to the Xp22.13-Xp21.2 region, Three candidate genes i n this region were investigated: the cDNA for kinase Rsk-2 involved in Coff in-Lowry syndrome, the brain-specific exon of a transcript in the DMD locus (DP140 isoform of dystrophin), and exon 18 of the glycerol kinase gene, wh ich is specific to fetal brain transcripts. All three sequences were normal . Am. J, Med, Genet. 83:132-137, 1999, (C) 1999 Wiley-Liss, Inc.