title: Determination of the gene structure of human oligophrenin-1 and identification of three novel polymorphisms by screening of DNA from 164 patients with non-specific X-linked mental retardation.
abstract: We have recently shown that mutations in oligophrenin-1 (OPHN1) are responsible for non-specific X-linked mental retardation (MRX). The structure of the gene encoding the OPHN1 protein was determined by isolation of genomic DNA clones from the human cosmid library. Genomic fragments containing exons were sequenced, and the sequences of the exons and flanking introns were defined. Knowledge of the genomic structure of the OPHN1 gene, which spans at least 500 kb and consists of 25 exons, will facilitate the search for additional mutations in OPHN1. OPHN1 was screened for mutations in 164 subjects with non-specific mental retardation. Three nucleotide substitutions were identified, one of which was a silent mutation in the codon threonine 301 at position 903 (G-->C). The other substitutions were located in exon 2, a G-->A substitution at position 133 (A45T), and in exon 10, a C-->T substitution at position 902 (T301M), but these are common polymorphisms rather than disease-causing mutations.
authors.affiliation: Inserm U129-ICGM, faculté de médecine Cochin, 27, rue du Faubourg Saint Jacques, 75014, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Billuart
authors.forename: J
authors.initials: J
authors.lastname: Chelly
authors.forename: A
authors.initials: A
authors.lastname: Carrié
authors.forename: M
authors.initials: M
authors.lastname: Vinet
authors.forename: P
authors.initials: P
authors.lastname: Couvert
authors.forename: N
authors.initials: N
authors.lastname: McDonell
authors.forename: R
authors.initials: R
authors.lastname: Zemni
authors.forename: A
authors.initials: A
authors.lastname: Kahn
authors.forename: C
authors.initials: C
authors.lastname: Moraine
authors.forename: C
authors.initials: C
authors.lastname: Beldjord
authors.forename: T
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002881:Chromosomes, Human, Pair 12; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D005091:Exons; D020690:GTPase-Activating Proteins; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D003598:Cytoskeletal Proteins; D017931:DNA Primers; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C111952:OPHN1 protein, human; D010750:Phosphoproteins