GENOTYPE/ PHENOTYPE RELATIONSHIPS IN FRAGILE X FAMILIES

脆性X综合征（FXS）是最常见的已知遗传性精神发育迟滞的原因，但它也可以表现为智商在正常范围内的个体的广泛行为和学习问题。 这项基因型-表型研究详细评估了前突变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FMR 1基因的总体CGG重复数、甲基化程度、信使RNA水平和FMR 1蛋白（FMRP）水平。 此外，在女性中，还评估了活化率（AR），其测量在活性X染色体上具有正常FMR 1基因的细胞的百分比。 本研究在两个中心进行：丹佛，科罗拉多和墨尔本，澳大利亚。 在澳大利亚，Danuta Loesch博士和Richard Huggins博士的专业知识包括定量谱系评估，这将使我们深入了解背景遗传效应如何改变脆性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.