Fragile X syndrome: a hypothesis regarding the molecular mechanism of the phenotype.
Fragile X syndrome: a hypothesis regarding the molecular mechanism of the phenotype.
复制标题
脆性 X 综合征：关于表型分子机制的假设。
DOI：
10.1002/ajmg.1320300169
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Warren,ST
中科院分区：
文献类型：
--
作者：
Warren,ST
在目前已知的所有人类染色体脆弱位点中，定位到Xq27.3的脆弱位点是唯一与异常表型相关的脆弱位点。这种表型被称为 Martin-Bell 或脆性 X 综合征，其最重要的表现是智力低下。我们认为该位点与异常表型相关，因为它位于 X 染色体上，特别是靠近 q 端粒。因此，如果在 fra(X) 雄性中随着 Xq28 的丢失而发生体内断裂，则该细胞对于脆弱位点远端的基因将是无效体的。类似地，如果断裂发生在活性 X 上，雌性细胞将在功能上无效。其他脆弱位点遗传物质的断裂和丢失要么由于同源基因的互补而没有影响，要么如果 X 连锁显着缺失（即 fra(Xq22)），则将是致命的。这导致有人提出脆性 X 综合征是由于远端基因的断层缺失造成的。我们在下面描述该模型的含义以及检验该假设的方法。
Among all the human chromosomal fragile sites currently recognized, the fragile site mapping to Xq27.3 is the only one associated with an abnormal phenotype. This phenotype, referred to as the Martin‐Bell or fragile X syndrome, has mental retardation as its most important manifestation. We propose that this site is associated with an abnormal phenotype due its location on the X chromosome, particularly it's proximity to the q telomere. Thus, if anin vivobreak should occur with loss of Xq28 in the fra(X) male, the cell would be nullisomic for the genes distal to the fragile site. Similarly, a female cell would be functionally nullisomic if the break occurred on the active X. Breakage and loss of genetic material at other fragile sites either would have no impact due to complementation by homologous genes or would be lethal if X‐linked with a significant deletion (i.e. fra(Xq22)). This leads to the proposal that the fragile X syndrome is due tomosaic nullisomyof distal genes. We describe below the implications of this model and a means to test this hypothesis.