Department of Clinical Genetics, Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
Psychiatry Res. 2015 Feb 28;225(3):268-75. doi: 10.1016/j.psychres.2014.12.028. Epub 2014 Dec 30.
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder with a strong genetic etiology; however, finding of candidate genes is hampered by its genetic heterogeneity and the influence of non-genetic factors on disease pathogenesis. We report a case of a male patient with GTS, obsessive compulsive disorder, attention-deficit/hyperactivity-disorder, as well as other comorbidities, and a translocation t(3;9)(q25.1;q34.3) inherited from a mother with tics. Mate-pair sequencing revealed that the translocation breakpoints truncated the olfactomedin 1 (OLFM1) gene and two uncharacterized transcripts. Reverse-transcription PCR identified several fusion transcripts in the carriers, and OLFM1 expression was found to be high in GTS-related human brain regions. As OLFM1 plays a role in neuronal development it is a likely candidate gene for neuropsychiatric disorders and haploinsufficiency of OLFM1 could be a contributing risk factor to the phenotype of the carriers. In addition, one of the fusion transcripts may exert a dominant-negative or gain-of-function effect. OLFM1 is unlikely to be a major GTS susceptibility gene as no point mutations or copy number variants affecting OLFM1 were identified in 175 additional patients. The translocation described is thus a unique event, but further studies in larger cohorts are required to elucidate involvement of OLFM1 in GTS pathogenesis.
图雷特综合征（Gilles de la Tourette syndrome，GTS）是一种具有强烈遗传病因的神经精神疾病；然而，候选基因的发现受到其遗传异质性和非遗传因素对疾病发病机制影响的阻碍。我们报告了一例男性患者，患有 GTS、强迫症、注意力缺陷/多动障碍以及其他合并症，并且从一位有抽搐的母亲那里遗传了易位 t(3;9)(q25.1;q34.3)。mate-pair 测序显示易位断点截断了嗅觉素 1（olfactomedin 1，OLFM1）基因和两个未被描述的转录本。逆转录 PCR 在携带者中鉴定出几种融合转录本，并且在与 GTS 相关的人类大脑区域中发现 OLFM1 表达较高。由于 OLFM1 在神经元发育中起作用，因此它是神经精神疾病的候选基因，并且 OLFM1 的单倍不足可能是携带者表型的一个促成风险因素。此外，其中一种融合转录本可能发挥显性负或获得性功能效应。由于在另外 175 名患者中未发现影响 OLFM1 的点突变或拷贝数变异，因此 OLFM1 不太可能是 GTS 的主要易感基因。所描述的易位是一个独特的事件，但需要在更大的队列中进行进一步研究，以阐明 OLFM1 在 GTS 发病机制中的作用。
