SLITRK1基因中的序列变异与妥瑞氏症有关。

Sequence variants in SLITRK1 are associated with Tourette's syndrome.

作者信息

Abelson Jesse F, Kwan Kenneth Y, O'Roak Brian J, Baek Danielle Y, Stillman Althea A, Morgan Thomas M, Mathews Carol A, Pauls David L, Rasin Mladen-Roko, Gunel Murat, Davis Nicole R, Ercan-Sencicek A Gulhan, Guez Danielle H, Spertus John A, Leckman James F, Dure Leon S, Kurlan Roger, Singer Harvey S, Gilbert Donald L, Farhi Anita, Louvi Angeliki, Lifton Richard P, Sestan Nenad, State Matthew W

机构信息

Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.

出版信息

Science. 2005 Oct 14;310(5746):317-20. doi: 10.1126/science.1116502.

DOI:10.1126/science.1116502

PMID:16224024

Abstract

Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS.

摘要

图雷特综合征（TS）是一种受遗传影响的发育性神经精神疾病，其特征为慢性发声和运动抽动。由于位于13q31.1染色体上的Slit和Trk样蛋白1（SLITRK1）与一名患图雷特综合征儿童的新生染色体倒位位置接近，我们将其作为候选基因进行研究。在174名无血缘关系的先证者中，我们在微小RNA hsa-miR-189的结合位点鉴定出一个移码突变和两个相同变异的独立发生情况。在3600条对照染色体中未发现这些变异。SLITRK1信使核糖核酸（mRNA）和hsa-miR-189在先前与图雷特综合征相关的脑区呈现重叠表达模式。野生型SLITRK1而非移码突变体可增强原代神经元培养中的树突生长。总体而言，这些发现支持罕见的SLITRK1序列变异与图雷特综合征之间的关联。