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

脆性X染色体综合征是最常见的遗传性精神发育迟滞。这种异常基因通过母亲的X染色体传给儿子或女儿。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遗传给女儿，就不会恶化。因此，受影响的孩子的祖父在他们的母亲一边，以及母亲，可能携带轻度异常基因（前突变），不足以导致智力迟钝。然而，最近发现，这些祖父可能会在晚年发展出震颤、不协调、动作缓慢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，即使另一条有前突变。但最近的报告表明，他们也可能发展FXTAS综合征，以及更年期提前。本研究的目的是了解这些异常在携带前突变的女性中有多常见和严重，使用临床，MRI和电子测量，并将异常与基因功能障碍和家族易感性的严重程度联系起来。

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.