Prevalence and genetic mechanisms of neurological and gynaecological changes in women carrying small FMR1 expansions

携带小 FMR1 扩增的女性神经和妇科变化的患病率和遗传机制

• 批准号: nhmrc : 436787
• 负责人: Dr Danuta Loesch
• 金额: $ 27.47万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/prevalence-genetic-mechanisms-fmr1-expansions/82399
• 关键词: Prevalence; genetic; mechanisms; neurological; gynaecological

Fragile X syndrome is one of the commonest genetic forms of mental retardation. The abnormal gene is passed from mothers to their sons or daughters, on their X chromosome. The gene abnormality is unstable, tending to worsen each time it is passed on. But if this gene abnormality is passed from fathers to their daughters, it does not worsen. Therefore, grandfathers of the affected children on their mother's side, as well as the mothers, may carry a mildly abnormal gene (a premutation), insufficient to cause mental retardation. However, it has recently been discovered that these grandfathers may develop a syndrome (FXTAS) of tremor, incoordination, slowness of movements and mild dementia in their later years. Women were thought to be protected, as they carry TWO X chromosomes, one of which is normal even if the other has a premutation. But very recent reports suggest that they may also develop the FXTAS syndrome, as well as early menopause. This study aims to see how common and severe these abnormalities are in women who carry the premutation, using clinical, MRI and electronic measurements, and to relate the abnormalities to the severity of the gene malfunction and familial predisposition.

脆性X染色体综合征是一种最常见的智力迟钝的遗传形式。这种异常基因通过X染色体从母亲传给儿子或女儿。这种基因异常是不稳定的，每次遗传都会恶化。但如果这种基因异常从父亲传给女儿，情况就不会恶化。因此，受影响的孩子的祖父在他们母亲的身边，以及母亲，可能携带轻微的异常基因（一种前兆），不足以导致智力迟钝。然而，最近发现，这些祖父在晚年可能会出现震颤、不协调、行动迟缓和轻度痴呆的综合征（FXTAS）。女性被认为是受保护的，因为她们携带两条X染色体，其中一条是正常的，即使另一条有突变。但最近的报告显示，她们也可能患上FXTAS综合征，以及提前绝经。这项研究的目的是通过临床、核磁共振成像和电子测量来了解这些异常在携带前置突变的女性中有多普遍和严重，并将这些异常与基因故障的严重程度和家族易感性联系起来。