Molecular genetic study of japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X)

Am J Med Genet. 2000 Sep 18;94(3):242-8.


X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) is one of the many known X-linked mental retardation syndromes. Mutations in the ATR-X gene (ATRX) that encodes a putative global transcription factor have been identified in patients with ATR-X as well as those with other forms of X-linked mental retardation syndrome. To better understand the genetic basis of ATR-X, we investigated nine patients with the ATR-X phenotype from eight independent Japanese families for mutations in ATRX. We identified seven missense mutations, including six novel mutations, all of which were located either in the N-terminal region corresponding to the putative zinc finger domain (N179S, P190L, V194I, and R246C) or in the C-terminal region corresponding to the helicase domain (V1552F, L1645S, and Y1847C). R246C was found in two independent patients. Furthermore, we investigated the origin of the mutations in seven mothers. Five mothers were found to be carriers, and two were not, indicating de novo origin of the mutations. When we compared clinical manifestations with respective mutations, we could not find apparent phenotype-genotype correlation. Therefore, the putative zinc finger domain and the helicase domains may have similar functional significance for the function of ATRX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Child
  • Child, Preschool
  • Chromatin / genetics
  • DNA Helicases*
  • DNA Mutational Analysis
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Family Health
  • Female
  • Genetic Linkage*
  • Genotype
  • Heterozygote
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Japan
  • Male
  • Mutation, Missense
  • Nuclear Proteins*
  • Pedigree
  • Phenotype
  • Protein Structure, Tertiary
  • Syndrome
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • X Chromosome*
  • X-linked Nuclear Protein
  • Zinc Fingers
  • alpha-Thalassemia / genetics*


  • Chromatin
  • DNA, Complementary
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • DNA Helicases
  • ATRX protein, human
  • X-linked Nuclear Protein