Bell M V, Hirst M C, Nakahori Y, MacKinnon R N, Roche A, Flint T J, Jacobs P A, Tommerup N, Tranebjaerg L, Froster-Iskenius U
Molecular Genetics Group, John Radcliffe Hospital, Oxford, England.
Cell. 1991 Feb 22;64(4):861-6. doi: 10.1016/0092-8674(91)90514-y.
The most common genetic cause of mental retardation after Down's syndrome, the fragile X syndrome, is associated with the occurrence of a fragile site at Xq27.3. This X-linked disease is intriguing because transmission can occur through phenotypically normal males. Theories to explain this unusual phenomenon include genomic rearrangements and methylation changes associated with a local block of reactivation of the X chromosome. Using microdissected markers close to the fragile site, we have been able to test these hypotheses. We present evidence for the association of methylation with the expression of the disease. However, there is no simple relationship between the degree of methylation and either the level of expression of the fragile site or the severity of the clinical phenotype.
除唐氏综合征外，最常见的导致智力迟钝的遗传病因——脆性X综合征，与Xq27.3处的一个脆性位点的出现有关。这种X连锁疾病很有意思，因为它可以通过表型正常的男性进行传播。解释这一异常现象的理论包括与X染色体局部再激活受阻相关的基因组重排和甲基化变化。利用靠近脆性位点的显微切割标记，我们得以检验这些假说。我们提供了甲基化与疾病表达相关的证据。然而，甲基化程度与脆性位点的表达水平或临床表型的严重程度之间并没有简单的关系。
