Machado-Ferreira Maria do Carmo, Costa-Lima Marcelo A, Boy Raquel T, Esteves Gabriela S, Pimentel Márcia M G
Department of Cell Biology and Genetics, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Am J Med Genet A. 2004 Apr 30;126A(3):237-40. doi: 10.1002/ajmg.a.20585.
Fragile X syndrome (FRAXA) is the most common form of inherited mental retardation (MR). The mutational mechanism leading to the disease involves an expansion of a trinucleotide repeat located at the 5' UTR region of the gene FMR-1. Four types of alleles can be identified in the population, based on the number of repeats: normal (6-40), gray-zone (41-60), premutated (61-200), and fully mutated (>200). Despite only full mutations being associated with the development of the disorder, some authors propose a correlation between FRAXA premutation and the occurrence of premature ovarian failure (POF). We have undertaken a study in 58 women from 24 fragile X syndrome families ascertained for FRAXA testing. Using Southern blotting for direct DNA analysis we have identified 19 normal, 33 premutation carriers, and 6 fully mutated individuals (including 4 somatic mosaics showing premutated and fully mutated alleles). Among the premutated women, 11 experienced menopause before the age of 40 (POF), including one somatic mosaic, which was different from the ones with normal pattern who did not experience POF. Our data corroborate the notion that females carrying alleles in the premutation range are at high risk of experiencing POF.
脆性X综合征（FRAXA）是遗传性智力迟钝（MR）最常见的形式。导致该疾病的突变机制涉及位于FMR - 1基因5'非翻译区的三核苷酸重复序列的扩增。根据重复序列的数量，在人群中可鉴定出四种类型的等位基因：正常（6 - 40）、灰色区域（41 - 60）、前突变（61 - 200）和完全突变（>200）。尽管只有完全突变与该疾病的发生相关，但一些作者提出FRAXA前突变与卵巢早衰（POF）的发生之间存在关联。我们对来自24个进行FRAXA检测的脆性X综合征家庭的58名女性进行了一项研究。通过Southern印迹法进行直接DNA分析，我们鉴定出19名正常个体、33名前突变携带者和6名完全突变个体（包括4名显示前突变和完全突变等位基因的体细胞嵌合体）。在前突变女性中，11人在40岁之前经历了绝经（POF），其中包括一名体细胞嵌合体，这与未经历POF的正常模式女性不同。我们的数据证实了携带前突变范围内等位基因的女性有患POF的高风险这一观点。
