Gibbons R J, Picketts D J, Villard L, Higgs D R
Medical Research Council Molecular Haematology Unit, John Radcliffe Hospital, Headington, Oxford, England.
Cell. 1995 Mar 24;80(6):837-45. doi: 10.1016/0092-8674(95)90287-2.
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.
ATR-X综合征是一种X连锁疾病，包括严重的精神运动发育迟缓、特征性面部特征、生殖器异常和α地中海贫血。我们已经表明，ATR-X是由XH2的多种突变引起的，XH2是解旋酶超家族一个亚组的成员，该亚组包括参与广泛细胞功能的蛋白质，如DNA重组和修复（RAD16、RAD54和ERCC6）以及转录调控（SW12/SNF2、MOT1和brahma）。复杂的ATR-X表型表明，XH2发生突变时会下调包括α珠蛋白基因在内的多个基因的表达，这表明它可能是一种全局转录调节因子。除了在ATR-X综合征中的作用外，XH2可能是定位到Xq13的其他形式X连锁智力迟钝的一个良好候选基因。
