Wöhrle D, Hirst M C, Kennerknecht I, Davies K E, Steinbach P
Abteilung Klinische Genetik der Universität, Ulm, Federal Republic of Germany.
Hum Genet. 1992 Apr;89(1):114-6. doi: 10.1007/BF00207057.
The fragile X syndrome is one of the most common familial causes of mental retardation. It is associated with the expression of a fragile site at Xq27.3, although not all individuals carrying the mutation are fragile-X-positive. Recently, the mutation causing this disease has been identified as the amplification of, or insertion into, a CGG repeat sequence at the fragile site. The mutated chromosome can be recognised by the decrease in mobility of the EcoRI fragment that covers the mutated region. Analysis of lymphocytes of affected males often gives a number of different sized fragments indicating somatic heterogeneity. We have investigated this mosaicism in various tissues of an affected fetus in order to determine the extent of the variation between tissues, and to ascertain how to interpret the results in lymphocytes. Our results suggest that the heterogeneity occurs in all fetal tissues, but that the pattern of fragments observed varies between tissues. Methylation across the region also varies. These differences may be reflected in the cellular phenotypes and may influence the ultimate expression of the clinical phenotype.
脆性X综合征是智力迟钝最常见的家族性病因之一。它与Xq27.3处脆性位点的表达相关，尽管并非所有携带该突变的个体都是脆性X阳性。最近，导致这种疾病的突变已被确定为脆性位点处CGG重复序列的扩增或插入。突变染色体可通过覆盖突变区域的EcoRI片段迁移率降低来识别。对受影响男性淋巴细胞的分析通常会产生许多不同大小的片段，表明存在体细胞异质性。我们研究了一名受影响胎儿各种组织中的这种嵌合现象，以确定组织间变异的程度，并确定如何解释淋巴细胞中的结果。我们的结果表明，异质性存在于所有胎儿组织中，但观察到的片段模式在不同组织间有所不同。该区域的甲基化情况也有所不同。这些差异可能反映在细胞表型中，并可能影响临床表型的最终表达。
