GENOTYPE/ PHENOTYPE RELATIONSHIPS IN FRAGILE X FAMILIES

脆性X染色体综合征（FXS）是已知最常见的智力迟钝的遗传原因，但它也可以表现为智商在正常范围内的个体的广泛的行为和学习问题。这项基因型-表型研究详细评估了突变前个体和完全突变个体的神经认知能力、情绪状态和身体特征。该信息与分子测量相关，包括FMR1基因的总体CGG重复数、甲基化程度、信使RNA水平和FMR1蛋白（FMRP）水平。此外，在女性中，激活率（AR）也被评估，它衡量的是活跃X染色体上具有正常FMR1基因的细胞的百分比。这项研究是在两个中心进行的：科罗拉多州的丹佛和澳大利亚的墨尔本。在澳大利亚，博士的专业知识。Danuta Loesch和Richard Huggins包括一个定量的谱系评估，这将使我们深入了解背景遗传效应如何改变脆弱的X表型。我们特别感兴趣的是临床参与是否真的存在于个体的前兆突变。

Fragile X syndrome (FXS) is the most common known inherited cause of mental retardation, but it can also manifest as a broad spectrum of behavior and learning problems in individuals with an IQ in the normal range. This genotype-phenotype study assesses in detail neurocognitive abilities, emotional status, and physical features in individuals with the premutation and in individuals with the full mutation. This information is correlated with molecular measures, including the overall CGG repeat number of the FMR1 gene, the degree of methylation, the messenger RNA levels, and the FMR1 protein (FMRP) levels. In addition, in females the activation ratio (AR) which measures the percentage of cells that have the normal FMR1 gene on the active X chromosome is also assessed. This study is carried out at two centers: Denver, Colorado and Melbourne, Australia. In Australia, the expertise of Drs. Danuta Loesch and Richard Huggins include a quantitative pedigree assessment that will give us insight to how background genetic effects modify the fragile X phenotype. We are particularly interested in whether clinical involvement truly exists in individuals with the premutation.