Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome).

Journal article

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.

Authors: Gibbons, R; Picketts, D; Villard, L; Higgs, D

• Publication status: Published
• Journal: Cell
• Volume: 80
• Issue: 6
• Pages: 837-845
• Publication date: 1995-03-01
• DOI: 10.1016/0092-8674(95)90287-2
• EISSN: 1097-4172
• ISSN: 0092-8674
• Language: English
• Keywords: DNA Repair; Chromosome Mapping; Gene Library; Molecular Sequence Data; Sequence Deletion; Syndrome; Lod Score; Amino Acid Sequence; Transcription, Genetic; X Chromosome; Humans; Genetic Linkage; Base Sequence; Conserved Sequence; Polymerase Chain Reaction; Fetus; Brain; DNA Helicases; Gene Expression Regulation; DNA Primers; alpha-Thalassemia; Abnormalities, Multiple; Multigene Family; Mental Retardation; Phenotype; Sequence Homology, Amino Acid