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

Linkage analysis was performed in three generations of a French family segregating a syndromal form of X‐linked mental retardation. All affected males had neonatal hypotonia, seizures, muscular hypodevelopment, and severe mental deficiency. A peak lod score of 2.90 at a recombination fraction of theta = 0 was detected for DXS 1052 and DXS 451 (Xp22.13). Recombination between the disease locus and the polymorphic markers in DXS7163 and DXS1238 suggested a gene mapping to the Xp22.13–Xp21.2 region. Three candidate genes in this region were investigated: the cDNA for kinase Rsk‐2 involved in Coffin‐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, which is specific to fetal brain transcripts. All three sequences were normal. Am. J. Med. Genet. 83:132–137, 1999. © 1999 Wiley‐Liss, Inc.