title: Mutational analysis of the ATRX gene by DGGE: a powerful diagnostic approach for the ATRX syndrome.
abstract: Molecular defects affecting the ATRX gene lead to the ATRX syndrome (alpha thalassemia/mental retardation syndrome, X-linked), characterized by severe mental retardation, microcephaly, distinct facial dysmorphism, and genital abnormalities, as well as a wide spectrum of other pathological features. Alpha thalassemia is frequent but does not represent a constant characteristic of the syndrome. An expanding phenotype of the ATRX gene (a RAD54 homologue encoding a putative zinc-finger helicase) has been demonstrated as a result of the association of single mutations with specific X-linked mental retardation syndromes. To date, mutational analysis of the gene has been based on direct DNA sequencing or using methods with a lower detection rate. In this paper, we present a broad-range DGGE method for single-step mutation scanning of the entire open reading frame (ORF) and canonical splice sites of the gene. Using this method, we successfully identified five novel sequence changes in the ATRX gene, including four missense mutations (K1733E, R2085C, D2136N, T2169A) and one polymorphism (IVS5+35G>A).
authors.affiliation: Laboratorio di Patologia Genetica, IRCCS Oasi Maria SS, Troina (EN), Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Borgione
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sturnio
authors.forename: Angela
authors.initials: A
authors.lastname: Spalletta
authors.forename: Maria
authors.initials: M
authors.lastname: Angela Lo Giudice
authors.forename: Lucia
authors.initials: L
authors.lastname: Castiglia
authors.forename: Ornella
authors.initials: O
authors.lastname: Galesi
authors.forename: Angela
authors.initials: A
authors.lastname: Ragusa
authors.forename: Marco
authors.initials: M
authors.lastname: Fichera
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods*; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000150:complications; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D012680:Sensitivity and Specificity; D013577:Syndrome; D000075924:X-linked Nuclear Protein; D017085:alpha-Thalassemia / Q000150:complications
chemical_list: D009687:Nuclear Proteins; D004247:DNA; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein