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

• Published in: American journal of medical genetics. Part A Vol. 118A; no. 3; pp. 217 - 222
• Main Authors: Annunziata, Ida, Lanzara, Carmela, Conte, Ivan, Zullo, Alberto, Ventruto, Valerio, Rinaldi, Maria Michela, D'Urso, Michele, Casari, Giorgio, Ciccodicola, Alfredo, Miano, Maria Giuseppina
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 30-04-2003
• Subjects: 5-Aminolevulinate Synthetase - genetics; Alleles; Centrosome - ultrastructure; Chromosome Mapping; Chromosomes, Human, X; Cytoskeletal Proteins; Databases as Topic; DNA Mutational Analysis; Ephrin-B1 - genetics; Exons; Family Health; Female; Genetic Linkage; Genotype; GTPase-Activating Proteins; Haplotypes; Humans; linkage analysis; Lod Score; Male; Mental Retardation, X-Linked - genetics; Models, Genetic; MRX candidate genes; MRX81; nonspecific X mental retardation; Nuclear Proteins - genetics; Pedigree; Phosphoproteins - genetics; Recombination, Genetic; Xp11.2-Xq12
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.10144

X‐linked nonspecific mental retardation (MRX) accounts for ∼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. © 2003 Wiley‐Liss, Inc.