title: Evidence that SIZN1 is a candidate X-linked mental retardation gene.
abstract: An estimated 1-3% of individuals within the United States are diagnosed with mental retardation (MR), yet the cause is unknown in nearly 50% of the patients. While several environmental, genetic and combined teratogenetic etiologies have been identified, many causative genes remain to be identified. Furthermore, the pathogenetic mechanisms underlying MR are known for very few of these genes. Males have a much higher incidence of MR implicating genes on the X-chromosome. We have recently identified a novel gene, SIZN1, on the X-chromosome and showed that it functions in modulating the BMP signaling pathway. Furthermore, we have shown this gene is necessary for basal forebrain cholinergic neuron (BFCN) specific gene expression. Given that cognitive function is impaired when BFCNs are lost or functionally disrupted, we undertook a screen of cognitively impaired males for SIZN1 mutations. We report on four different sequence variants in SIZN1 in 11 individuals with nonsyndromic X-linked mental retardation (XLMR). Our data implicate SIZN1 as a candidate gene for XLMR and/or as a neurocognitive functional modifier.
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ginam
authors.initials: G
authors.lastname: Cho
authors.forename: Shambhu S
authors.initials: SS
authors.lastname: Bhat
authors.forename: Jinsong
authors.initials: J
authors.lastname: Gao
authors.forename: Julianne S
authors.initials: JS
authors.lastname: Collins
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Rogers
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Simensen
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
authors.forename: Anand K
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D003071:Cognition; D014644:Genetic Variation; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016548:Prosencephalon / Q000503:physiopathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins; D014157:Transcription Factors; C532851:ZCCHC12 protein, human
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