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

Abstract

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.

Systematic analysis of X-inactivation in 19 XLMR families: extremely skewed profiles in carriers in three families

“…Inactivation studies of two of the 16 families have previously been reported, along with the clinical and linkage findings. 8,9 …”

Increasing evidence for a new X-linked mental retardation/epilepsy gene localized to Xp21.3-Xp22.1

“…Molecular studies using polymorphic microsatellite markers of chromosome X allowed us to determine the locus to be between marker DXS1226 and the adrenal hypoplasia locus in a 7-cM interval contained in the interval previously reported by Claes et al [1997] and Ronce et al [1999]. The marker DXS451, for which the two-point lod score with the XLMR gene was established to be 2.90 at a of 0.0, is contained between the two recombinations we de-scribed.…”

“…We wish to draw attention to four phenotypically similar families that were reported previously and described as an X-linked form of infantile spasms [Feinberg and Leahy, 1977;Rugtveit, 1986;Claes et al, 1997]. The affected males of these latter families [Ronce et al, 1999] presented with severe mental deficiency associated with early-onset intractable seizures typical of infantile spasms in most but not all cases.…”

“…We read with interest the article, published recently in this journal by Ronce et al [1999] describing three generations of a French family segregating with a syndromal form of X-linked mental retardation (XLMR) characterized by hypotonia, intractable seizures, and severe mental deficiency. We wish to draw attention to four phenotypically similar families that were reported previously and described as an X-linked form of infantile spasms [Feinberg and Leahy, 1977;Rugtveit, 1986;Claes et al, 1997].…”

“…The marker DXS451, for which the two-point lod score with the XLMR gene was established to be 2.90 at a of 0.0, is contained between the two recombinations we de-scribed. Therefore, it is likely that the French family described by Ronce et al [1999] represents a disorder allelic to, or perhaps even typical of, the disorder increasingly recognized as X-linked West syndrome.…”