title: Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without alpha-thalassemia.
abstract: We have previously reported the isolation of a gene from Xq13 that codes for a putative regulator of transcription (XNP) and has now been shown to be the gene involved in the X-linked alpha-thalassemia with mental retardation (ATR-X) syndrome. The widespread expression and numerous domains present in the putative protein suggest that this gene could be involved in other phenotypes. The predominant expression of the gene in the developing brain, as well as its association with neuron differentiation, indicates that mutations of this gene might result in a mental retardation (MR) phenotype. In this paper we present a family with a splice junction mutation in XNP that results in the skipping of an exon and in the introduction of a stop codon in the middle of the XNP-coding sequence. Only the abnormal transcript is expressed in two first cousins presenting the classic ATR-X phenotype (with alpha-thalassemia and HbH inclusions). In a distant cousin presenting a similar dysmorphic MR phenotype but not having thalassemia, approximately 30% of the XNP transcripts are normal. These data demonstrate that the mode of action of the XNP gene product on globin expression is distinct from its mode of action in brain development and facial morphogenesis and suggest that other dysmorphic mental retardation phenotypes, such as Juberg-Marsidi or some sporadic cases of Coffin-Lowry, could be due to mutations in XNP.
authors.affiliation: INSERM U406, Marseille, France.
authors.forename: L
authors.initials: L
authors.lastname: Villard
authors.forename: A
authors.initials: A
authors.lastname: Toutain
authors.forename: A M
authors.initials: AM
authors.lastname: Lossi
authors.forename: J
authors.initials: J
authors.lastname: Gecz
authors.forename: C
authors.initials: C
authors.lastname: Houdayer
authors.forename: C
authors.initials: C
authors.lastname: Moraine
authors.forename: M
authors.initials: M
authors.lastname: Fontès
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D004265:DNA Helicases; D004303:Dosage Compensation, Genetic; D005260:Female; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000097:blood; D013577:Syndrome; D014960:X Chromosome; D000075924:X-linked Nuclear Protein; D017085:alpha-Thalassemia / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein