title: A novel splicing mutation of the ATRX gene in ATR-X syndrome.
abstract: X-linked alpha-thalassemia/mental retardation syndrome (ATR-X, MIM#301040) is an X-linked recessive condition affecting males. ATR-X is characterized by severe mental retardation, mild HbH disease, dysmorphic facies, and genital and skeletal abnormalities. ATR-X is caused by mutations in the ATRX gene. Most mutations affect two functionally important domains, the ADD domain and the helicase domain. Here, we report on two brothers with the ATR-X phenotype without HbH disease; both had a mutation in the 5' upstream region of the ADD domain of the ATRX gene. This mutation was a G to T nucleotide substitution at the 3' end of exon 5 and resulted in splicing out of exons 5 and 6. Analysis of cDNA structure may clarify genotype-phenotype correlations in ATR-X because splicing mutation could be detectable only by cDNA analysis.
authors.affiliation: Department of Medical Genetics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan. twada@sch.md.shinshu-u.ac.jp
authors.forename: Takahito
authors.initials: T
authors.lastname: Wada
authors.forename: Masae
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Shinji
authors.initials: S
authors.lastname: Saitoh
mesh_terms: D000293:Adolescent; D000328:Adult; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D000075924:X-linked Nuclear Protein
chemical_list: D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein