Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome).
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.
Gibbons
R J
RJ
Medical Research Council Molecular Haematology Unit, John Radcliffe Hospital, Headington, Oxford, England.
Picketts
D J
DJ
Villard
L
L
Higgs
D R
DR
D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D017124:Conserved Sequence; D004265:DNA Helicases / Q000235:genetics*; D017931:DNA Primers; D004260:DNA Repair; D005333:Fetus; D005786:Gene Expression Regulation; D015723:Gene Library; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008126:Lod Score; D008969:Molecular Sequence Data; D005810:Multigene Family; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014158:Transcription, Genetic; D014960:X Chromosome; D017085:alpha-Thalassemia / Q000235:genetics*
D017931:DNA Primers; D004265:DNA Helicases