title: Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency.
abstract: Physical mapping of the breakpoints of a pericentric inversion of the X chromosome (46,X,inv[X][p21q27]) in a female patient with mild mental retardation revealed localization of the Xp breakpoint in the IL1RAPL gene at Xp21.3 and the Xq breakpoint near the SOX3 gene (SRY [sex determining region Y]-box 3) (GenBank accession number NM_005634) at Xq26.3. Because carrier females with microdeletion in the IL1RAPL gene do not present any abnormal phenotype, we focused on the Xq breakpoint. However, we were unable to confirm the involvement of SOX3 in the mental retardation in this female patient. To validate SOX3 as an X-linked mental retardation (XLMR) gene, we performed mutation analyses in families with XLMR whose causative gene mapped to Xq26-q27. We show here that the SOX3 gene is involved in a large family in which affected individuals have mental retardation and growth hormone deficiency. The mutation results in an in-frame duplication of 33 bp encoding for 11 alanines in a polyalanine tract of the SOX3 gene. The expression pattern during neural and pituitary development suggests that dysfunction of the SOX3 protein caused by the polyalanine expansion might disturb transcription pathways and the regulation of genes involved in cellular processes and functions required for cognitive and pituitary development.
authors.affiliation: Service de GénétiquehyphenINSERM U316, CHU Bretonneau, Tours, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laumonnier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ronce
authors.forename: Ben C J
authors.initials: BC
authors.lastname: Hamel
authors.forename: Paul
authors.initials: P
authors.lastname: Thomas
authors.forename: James
authors.initials: J
authors.lastname: Lespinasse
authors.forename: Martine
authors.initials: M
authors.lastname: Raynaud
authors.forename: Christine
authors.initials: C
authors.lastname: Paringaux
authors.forename: Hans
authors.initials: H
authors.lastname: Van Bokhoven
authors.forename: Vera
authors.initials: V
authors.lastname: Kalscheuer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Claude
authors.initials: C
authors.lastname: Moraine
authors.forename: Sylvain
authors.initials: S
authors.lastname: Briault
mesh_terms: D019457:Chromosome Breakage / Q000235:genetics; D007446:Chromosome Inversion; D041321:Chromosomes, Human, X / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008040:Genetic Linkage / Q000235:genetics; D006609:High Mobility Group Proteins / Q000235:genetics*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010455:Peptides / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D010455:Peptides; C527785:SOX3 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D019382:Human Growth Hormone; C019529:polyalanine