Hunter Jessica Ezzell, Allen Emily Graves, Abramowitz Ann, Rusin Michele, Leslie Mary, Novak Gloria, Hamilton Debra, Shubeck Lisa, Charen Krista, Sherman Stephanie L
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Whitehead Biomedical Research Building, Suite 301, Atlanta, GA 30322, USA.
Behav Genet. 2008 Sep;38(5):493-502. doi: 10.1007/s10519-008-9214-3. Epub 2008 Jun 6.
The fragile X disorder spectrum, due to a CGG expansion in FMR1, includes fragile X syndrome (>200 repeats) and the premutation-associated disorders of ovarian insufficiency and tremor/ataxia syndrome (approximately 55-199 repeats). Altered neurobehavioral profiles including variation of phenotypes associated with mood and anxiety may be expected among younger premutation carriers given this spectrum of disorders. However, previous studies have produced conflicting findings, providing the motivation to examine these phenotypes further. We investigated measures of mood and anxiety in 119 males and 446 females age 18-50 ascertained from families with a history of fragile X syndrome and from the general population. Scores were analyzed using a linear model with repeat length as the main predictor, adjusting for potential confounders. Repeat length was not associated with anxiety, but was marginally associated with depression and negative affect in males and negative affect only in females. These results suggest that premutation carriers may be at risk for emotional morbidity; however, phenotypic differences were subtle and of small effect size.
由于FMR1基因中CGG重复序列扩增导致的脆性X障碍谱系，包括脆性X综合征（>200次重复）以及与卵巢功能不全和震颤/共济失调综合征相关的前突变（约55 - 199次重复）。鉴于这种障碍谱系，预计在较年轻的前突变携带者中会出现包括与情绪和焦虑相关的表型变异在内的神经行为特征改变。然而，先前的研究结果相互矛盾，这促使我们进一步研究这些表型。我们调查了119名年龄在18 - 50岁的男性和446名年龄在18 - 50岁的女性的情绪和焦虑指标，这些参与者来自有脆性X综合征家族史的家庭以及普通人群。使用以重复长度作为主要预测因子的线性模型对得分进行分析，并对潜在混杂因素进行调整。重复长度与焦虑无关，但与男性的抑郁和消极情绪以及仅与女性的消极情绪存在微弱关联。这些结果表明，前突变携带者可能存在情绪发病风险；然而，表型差异细微且效应量较小。
