Vittal Padmaja, Pandya Shrikant, Sharp Kevin, Berry-Kravis Elizabeth, Zhou Lili, Ouyang Bichun, Jackson Jonathan, Hall Deborah A
Department of Neurosciences (P.V.), Northwestern Medicine Regional Medical Group, Winfield, IL; the Department of Bioengineering (S.P.), University of Illinois at Chicago; the Department of Pediatrics, Neurological Sciences, Biochemistry (K.S., E.B.-K., L.Z., J.J.), and the Department of Neurological Sciences (B.O., D.A.H.), Rush University Medical Center, Chicago, IL.
Neurol Genet. 2018 Jul 27;4(4):e246. doi: 10.1212/NXG.0000000000000246. eCollection 2018 Aug.
To explore the association of a splice variant of the () gene, loss of () AGG interspersions and CGG repeat size with manifestation, and severity of clinical symptoms of fragile X-associated tremor/ataxia syndrome (FXTAS).
Premutation carriers (PMCs) with FXTAS, without FXTAS, and normal controls (NCs) had a neurologic evaluation and collection of skin and blood samples. Expression of transcript/splice variant 2 (-TV2), nonspliced , total , and messenger RNA were quantified and compared using analysis of variance. Least absolute shrinkage and selection operator (LASSO) logistic regression and receiver operating characteristic analyses were performed.
Premutation men and women both with and without FXTAS had higher -TV2 levels compared with NC men and women (n = 135,135, < 0.0001), and -TV2 had good discriminating power for FXTAS compared with NCs but not for FXTAS from PMC. After adjusting for age, loss of AGG, larger CGG repeat size (in men), and elevated -TV2 level (in women) were strongly associated with FXTAS compared with NC and PMC (combined).
This study found elevated levels of and loss of AGG interruptions in both men and women with FXTAS. Future studies will be needed to determine whether these variables can provide useful diagnostic or predictive information.
探讨（）基因的剪接变体、（）AGG 间隔缺失及 CGG 重复序列大小与脆性 X 相关震颤/共济失调综合征（FXTAS）临床症状的表现及严重程度之间的关联。
对患有 FXTAS 的前突变携带者（PMCs）、未患 FXTAS 的 PMCs 以及正常对照者（NCs）进行神经学评估，并采集皮肤和血液样本。使用方差分析对转录本/剪接变体 2（-TV2）、未剪接的、总、信使 RNA 的表达进行定量和比较。进行最小绝对收缩和选择算子（LASSO）逻辑回归及受试者工作特征分析。
与 NC 男性和女性相比，患有和未患 FXTAS 的前突变男性和女性的 -TV2 水平均较高（n = 135,135，< 0.0001），与 NCs 相比，-TV2 对 FXTAS 具有良好的判别能力，但对来自 PMC 的 FXTAS 则不然。在调整年龄后，与 NC 和 PMC（合并）相比，AGG 缺失、较大的 CGG 重复序列大小（男性）以及升高的 -TV2 水平（女性）与 FXTAS 密切相关。
本研究发现 FXTAS 男性和女性中水平升高且存在 AGG 中断缺失。未来需要进一步研究以确定这些变量是否能提供有用的诊断或预测信息。
