title: Aberrant GRIA3 transcripts with multi-exon duplications in a family with X-linked mental retardation.
abstract: Investigation of chromosomal rearrangements in patients with mental retardation (MR) is particularly informative in the search for novel genes involved in MR. We report on a family with a genomic duplication at Xq25 identified by oligo array-CGH. Further characterization showed a partial tandem duplication of GRIA3 extending from exon 1 to exon 12. This duplication is present in two brothers with MR and on one allele in their sister with normal phenotype and completely skewed X-chromosome inactivation. The duplication is inherited from the mother, whose cognitive level is low and X-chromosome inactivation is random. This is the second family with partial duplication of GRIA3 associated with MR. GRIA3 expression studies in our case demonstrated a new mechanism for GRIA3 dysfunction with the presence of aberrant GRIA3 transcripts carrying multi-exon duplications leading to a frameshift. Our study gives additional support to the implication of GRIA3 in X-linked MR.
authors.affiliation: Nancy Université, EA 4002, Laboratoire de Génétique, Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Bonnet
authors.forename: B
authors.initials: B
authors.lastname: Leheup
authors.forename: M
authors.initials: M
authors.lastname: Béri
authors.forename: C
authors.initials: C
authors.lastname: Philippe
authors.forename: M-J
authors.initials: MJ
authors.lastname: Grégoire
authors.forename: P
authors.initials: P
authors.lastname: Jonveaux
mesh_terms: D001483:Base Sequence; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D018091:Receptors, AMPA / Q000235:genetics*; D049951:X Chromosome Inactivation; D055815:Young Adult
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3