Losekoot M, Hoogendoorn E, Olmer R, Jansen C C, Oosterwijk J C, van den Ouweland A M, Halley D J, Warren S T, Willemsen R, Oostra B A, Bakker E
MGC-Department of Human Genetics, Leiden University, The Netherlands.
J Med Genet. 1997 Nov;34(11):924-6. doi: 10.1136/jmg.34.11.924.
The fragile X syndrome, an X linked mental retardation syndrome, is caused by an expanded CGG repeat in the first exon of the FMR1 gene. In patients with an expanded repeat the FMR1 promoter is methylated and, consequently, the gene is silenced and no FMR1 protein (FMRP) is produced, thus leading to the clinical phenotype. Here we describe a prenatal diagnosis performed in a female from a fragile X family carrying a large premutation. In chorionic villus DNA of the male fetus the normal maternal CGG allele and a normal pattern on Southern blot analysis were found in combination with the FRAXAC2 and DXS297 allele of the maternal at risk haplotype. A second chorionic villus sampling was performed giving identical results on DNA analysis and, in addition, expression of FMRP was shown by immunohistochemistry. We concluded that the male fetus was not affected with the fragile X syndrome. Subsequent detailed haplotype analysis showed a complex recombination pattern resembling either gene conversion or a double crossover within a 20 kb genomic region.
脆性X综合征是一种X连锁智力低下综合征，由FMR1基因第一外显子中CGG重复序列扩增所致。在重复序列扩增的患者中，FMR1启动子发生甲基化，因此该基因沉默，不产生FMR1蛋白（FMRP），从而导致临床表型。本文描述了对一名来自脆性X家族、携带大的前突变的女性进行的产前诊断。在男性胎儿的绒毛膜绒毛DNA中，发现了正常的母源CGG等位基因以及Southern印迹分析中的正常模式，同时伴有母源风险单倍型的FRAXAC2和DXS297等位基因。进行了第二次绒毛膜绒毛取样，DNA分析结果相同，此外，免疫组织化学显示FMRP表达。我们得出结论，该男性胎儿未受脆性X综合征影响。随后详细的单倍型分析显示，在一个20 kb的基因组区域内存在类似于基因转换或双交换的复杂重组模式。
