Mornet E, Bogyo A, Deluchat C, Simon-Bouy B, Mathieu M, Thépot F, Grisard M C, Leguern E, Boué J, Boué A
Centre d'Etudes de Biologie Prénatale (CEBIOP), Château de Longchamp, Bois de Boulogne, Paris, France.
Hum Genet. 1993 Oct;92(4):373-8. doi: 10.1007/BF01247338.
The phenotypically normal sister of a patient affected by fragile X syndrome was referred for genetic counselling and was found to carry a mosaic karyotype 46,X,r(X)/45,X. Because the probability of the simultaneous chance occurrence of fragile X syndrome and a ring chromosome X in the same family is very low, we postulated that the breakpoint of the ring chromosome X originated in the cytogenetic break in Xq27.3 responsible for fragile X syndrome. In order to determine the relative positions of the breakpoint on the ring chromosome X and the (CGG)n unstable sequence responsible for the fragile X mutation, we used molecular markers to analyse the telomeric regions of chromosome X in this family. The results showed that the ring chromosome X was the maternal fragile X chromosome and that the telomeric deletion on the long arm encompassed the (CGG)n sequence. This suggests that the cytogenetic break in Xq27.3 is distinct from the unstable (CGG)n sequence, or that the break followed by the end-to-end fusion creating the ring chromosome was not completely conservative. Analysis of DNA markers on the short arm of chromosome X evidenced a deletion of a large part of the pseudoautosomal region, allowing us to position the genes involved in stature and in some syndromes associated with telomeric deletions of Xp on the proximal side of the pseudoautosomal region.
一名脆性X综合征患者表型正常的妹妹前来进行遗传咨询，结果发现其携带嵌合核型46,X,r(X)/45,X。由于在同一家族中同时偶然出现脆性X综合征和环形X染色体的概率非常低，我们推测环形X染色体的断点起源于导致脆性X综合征的Xq27.3细胞遗传学断裂处。为了确定环形X染色体上的断点与导致脆性X突变的(CGG)n不稳定序列的相对位置，我们使用分子标记分析了该家族中X染色体的端粒区域。结果显示，环形X染色体是母源脆性X染色体，长臂上的端粒缺失包含了(CGG)n序列。这表明Xq27.3处的细胞遗传学断裂与不稳定的(CGG)n序列不同，或者说断裂后通过端对端融合形成环形染色体的过程并非完全保守。对X染色体短臂上DNA标记的分析表明，假常染色体区域的很大一部分发生了缺失，这使我们能够将与身高以及一些与Xp端粒缺失相关综合征有关的基因定位在假常染色体区域的近端。
