Mapping of MRX81 in Xp11.2‐Xq12 suggests the presence of a new gene involved in nonspecific X‐linked mental retardation

Abstract

X-linked nonspecific mental retardation (MRX) accounts for approximately 25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene.

MRX87 family with Aristaless Xdup24bp mutation and implication for polyAlanine expansions

“…A standard set of microsatellite markers on the X chromosome, evenly spaced every 10 cM (ABI PRISM Linkage Mapping Sets vs2, Applied Biosystems) was PCR amplified using conditions already described [3]. Thirteen individuals of the family were genotyped (Figure 1) and PCR products were analysed on automatic sequencer (ABI PRISM 3100, Applied Biosystem).…”

“…Extra fluorescently labelled primers were synthesized for seven additional polymorphic markers chosen in public databases. Two-point linkage analysis was performed by the MLINK program version 5.1, from the LINKAGE software package [3]. The approved gene symbol MRX87 (Mental Retardation X-Linked 87) was assigned according to the HUGO (Human Genome Organization) nomenclature.…”

“…To date more than 50 XLMR genes have been recognized [1-3]. Each of them accounts for a very small proportion of the affected families with the exception of FMR1 , whose loss of function mutation causes the Fragile X syndrome, and the Aristaless X ( ARX ) gene mutated in several syndromic and non syndromic mentally retarded patients [4-9].…”

Targeted Deletion of CASK-Interacting Nucleosome Assembly Protein Causes Higher Locomotor and Exploratory Activities

“…Human CINAP is located at Xp11.2, and is included in the nonspecific X-linked mental retardation MRX81 locus (Xp11.2-Xq12) [22] . Although we previously determined that CINAP regulates NMDAR2b expression in cultured hippocampal neurons, NMDAR2b protein levels were not significantly changed in the brains of our CINAP knockout mice.…”

The Nucleosome Assembly Protein TSPYL2 Regulates the Expression of NMDA Receptor Subunits GluN2A and GluN2B

“…TSPYL2 is within the chromosome region linked to neurodevelopmental syndromes212223. In this study, we investigated whether TSPYL2 plays a role in cognitive function through transcriptional regulation of neuron-specific genes.…”