title: MRX87 family with Aristaless X dup24bp mutation and implication for polyAlanine expansions.
abstract: BACKGROUND
  Cognitive impairments are heterogeneous conditions, and it is estimated that 10% may be caused by a defect of mental function genes on the X chromosome. One of those genes is Aristaless related homeobox (ARX) encoding a polyA-rich homeobox transcription factor essential for cerebral patterning and its mutations cause different neurologic disorders. We reported on the clinical and genetic analysis of an Italian family with X-linked mental retardation (XLMR) and intra-familial heterogeneity, and provided insight into its molecular defect.
  
  
  METHODS
  We carried out on linkage-candidate gene studies in a new MRX family (MRX87). All coding regions and exon-intron boundaries of ARX gene were analysed by direct sequencing.
  
  
  RESULTS
  MRX87 patients had moderate to profound cognition impairment and a combination of minor congenital anomalies. The disease locus, MRX87, was mapped between DXS7104 and DXS1214, placing it in Xp22-p21 interval, a hot spot region for mental handicap. An in frame duplication of 24 bp (ARXdup24) in the second polyAlanine tract (polyA_II) in ARX was identified.
  
  
  CONCLUSIONS
  Our study underlines the role of ARXdup24 as a critical mutational site causing mental retardation linked to Xp22. Phenotypic heterogeneity of MRX87 patients represents a new observation relevant to the functional consequences of polyAlanine expansions enriching the puzzling complexity of ARXdup24-linked diseases.
authors.affiliation: Institute of Genetics and Biophysics Adriano Buzzati Traverso CNR, Naples, Italy. laperuta@igb.cnr.it
authors.forename: Carmela
authors.initials: C
authors.lastname: Laperuta
authors.forename: Letizia
authors.initials: L
authors.lastname: Spizzichino
authors.forename: Pio
authors.initials: P
authors.lastname: D'Adamo
authors.forename: Jlenia
authors.initials: J
authors.lastname: Monfregola
authors.forename: Antonio
authors.initials: A
authors.lastname: Maiorino
authors.forename: Angela
authors.initials: A
authors.lastname: D'Eustacchio
authors.forename: Valerio
authors.initials: V
authors.lastname: Ventruto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.forename: Michele
authors.initials: M
authors.lastname: D'Urso
authors.forename: Pietro
authors.initials: P
authors.lastname: Chiurazzi
authors.forename: Matilde Valeria
authors.initials: MV
authors.lastname: Ursini
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Miano
mesh_terms: D041321:Chromosomes, Human, X; D017931:DNA Primers; D020440:Gene Duplication; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010455:Peptides / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C469264:ARX protein, human; D017931:DNA Primers; D018398:Homeodomain Proteins; D010455:Peptides; D014157:Transcription Factors; C019529:polyalanine