Mutations in a Putative Global Transcriptional Regulator Cause X-linked Mental Retardation With Alpha-Thalassemia (ATR-X Syndrome)

Cell. 1995 Mar 24;80(6):837-45. doi: 10.1016/0092-8674(95)90287-2.

Abstract

The ATR-X syndrome is an X-linked disorder comprising severe psychomotor retardation, characteristic facial features, genital abnormalities, and alpha-thalassemia. We have shown that ATR-X results from diverse mutations of XH2, a member of a subgroup of the helicase superfamily that includes proteins involved in a wide range of cellular functions, including DNA recombination and repair (RAD16, RAD54, and ERCC6) and regulation of transcription (SW12/SNF2, MOT1, and brahma). The complex ATR-X phenotype suggests that XH2, when mutated, down-regulates expression of several genes, including the alpha-globin genes, indicating that it could be a global transcriptional regulator. In addition to its role in the ATR-X syndrome, XH2 may be a good candidate for other forms of X-linked mental retardation mapping to Xq13.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • Brain / metabolism
  • Chromosome Mapping
  • Conserved Sequence
  • DNA Helicases / genetics*
  • DNA Primers
  • DNA Repair*
  • Fetus
  • Gene Expression Regulation*
  • Gene Library
  • Genetic Linkage
  • Humans
  • Intellectual Disability / genetics*
  • Lod Score
  • Molecular Sequence Data
  • Multigene Family*
  • Phenotype
  • Polymerase Chain Reaction
  • Sequence Deletion*
  • Sequence Homology, Amino Acid
  • Syndrome
  • Transcription, Genetic*
  • X Chromosome*
  • alpha-Thalassemia / genetics*

Substances

  • DNA Primers
  • DNA Helicases

Associated data

  • GENBANK/X83753