title: Partial tandem duplication of GRIA3 in a male with mental retardation.
abstract: The genetic factors underlying mental retardation (MR) are very heterogeneous. Recent studies have identified a number of genes involved in MR, several of which lie on the X-chromosome, but the current understanding of the monogenic causes of MR is far from complete. Investigation of chromosomal rearrangements in patients with MR has proven particularly informative in the search for novel genes. Using array-based comparative genomic hybridization analysis, we identified a small copy number gain at Xq25, which was undetectable by conventional G-band analysis, in a boy with unexplained MR. Further characterization revealed a partial tandem duplication of GRIA3, an alteration also present on one allele in his mother. RT-PCR analysis of lymphoblastoid cell RNA revealed remarkably reduced GRIA3 transcript levels in the patient. The mother, whose cognitive level is normal, also demonstrated remarkably reduced GRIA3 transcript levels in lymphoblastoid cells, and X-chromosome inactivation (XCI) was completely skewed in her peripheral lymphocytes. It is possible that XCI in the brain is not completely skewed and that GRIA3 expression from the normal allele may account for the mother's normal cognitive function. Taken together with previous findings of GRIA3 disruptions in the patients with MR, our study strengthens the idea that GRIA3 is a candidate gene for X-linked MR and that severely reduced GRIA3 expression results in MR.
authors.affiliation: Division of Clinical Genetics, Department of Medical Genetics, Osaka University Graduate School of Medicine, 2-2-B9 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Chiyonobu
authors.forename: Shin
authors.initials: S
authors.lastname: Hayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Morimoto
authors.forename: Yuri
authors.initials: Y
authors.lastname: Miyanomae
authors.forename: Akira
authors.initials: A
authors.lastname: Nishimura
authors.forename: Akemi
authors.initials: A
authors.lastname: Nishimoto
authors.forename: Chiyomi
authors.initials: C
authors.lastname: Ito
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
mesh_terms: D001483:Base Sequence; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D018091:Receptors, AMPA / Q000235:genetics*; D014158:Transcription, Genetic; D049951:X Chromosome Inactivation
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3