Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3–p22.2 (MRX49) and Xp11.3–p11.21 (MRX50)

Abstract

Two families with nonspecific X-linked mental retardation (XLMR) are presented. In the first family, MRX49, 5 male patients in 2 generations showed mild to moderate mental retardation. Two-point linkage analysis with 28 polymorphic markers, dispersed over the X-chromosome, yielded a maximal LOD score of 2.107 with markers DXS7107 and DXS8051 at theta = 0.0, localizing the MRX49 gene at Xp22.3-p22.2, between Xpter and marker DXS8022. Multipoint linkage analysis showed negative LOD values over all other regions of the chromosome. In the second family, MRX50, 4 males in 2 generations showed moderate mental retardation. Pairwise linkage analysis with 28 polymorphic markers yielded a LOD score of 2.056 with markers DXS8054, DXS1055, and DXS1204, all at theta = 0.0. Flanking markers were DXS8012 and DXS991, situating the MRX50 gene at Xp11.3-Xp11.21, in the pericentromeric part of the short arm of the X chromosome.

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

“…In CLCN4 , that encodes the electrogenic chloride/proton exchanger ClC-4, 60 we discovered a protein truncating variant (p.Asp15Serfs*18, family MRX49 61 ) and four missense variants (p.Gly731Arg, family MRX15, 62 p.Leu221Val, p.Val536Met, p.Gly78Ser) (Figure 1a). ID of the affected males was variable, even within families, ranging from mild to severe.…”

Absence of learning difficulties in a hyperactive boy with a terminal Xp deletion encompassing the MRX49 locus

“…These analyses have included a clinical and molecular study of 27 patients with deletions involving the distal short arm of the X chromosome,1 a description by Schaefer et al 3 of several patients with LD and terminal and interstitial Xp deletions,3 and a two point linkage analysis with X chromosomal markers on a family in which five males in two generations showed mild to moderate LD 8…”

Telomeres: a diagnosis at the end of the chromosomes

“…138 139 One gene for short stature, the short stature homeobox containing gene (SHOX), 140 was also shown to be mutated or deleted in families with Leri-Weill dyschondrosteosis. 141 142 Although a putative locus for mental retardation (MRX49) has been located distal to the STS locus, 143 Tobias et al 144 reported a boy with a normal intelligence and a telomeric deletion including the STS locus as the result of a der(X)t(X;Y)(p22.31;q11.21). Clinically there is a much similarity with the case reported by De Vries et al 145 with a submicroscopic Xp22.31-pter deletion with a breakpoint just upstream of the STS locus.…”