Warren S T
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
Am J Med Genet. 1988 May-Jun;30(1-2):681-8. doi: 10.1002/ajmg.1320300169.
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 an in vivo break 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 to mosaic nullisomy of distal genes. We describe below the implications of this model and a means to test this hypothesis.
在目前已识别的所有人类染色体脆性位点中，定位于Xq27.3的脆性位点是唯一与异常表型相关的位点。这种表型被称为马丁 - 贝尔综合征或脆性X综合征，其最重要的表现是智力迟钝。我们认为，该位点与异常表型相关是由于其位于X染色体上，特别是它靠近q端粒。因此，如果在脆性X男性中发生体内断裂并导致Xq28缺失，细胞对于脆性位点远端的基因将成为缺体。同样，如果断裂发生在活性X染色体上，女性细胞在功能上也将成为缺体。在其他脆性位点的遗传物质断裂和丢失，要么由于同源基因的互补而没有影响，要么如果与显著缺失连锁在X染色体上（即fra(Xq22)）则会致死。这导致了脆性X综合征是由于远端基因的嵌合缺体这一观点。我们在下面描述该模型的影响以及检验这一假设的方法。
