Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism
Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism
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DOI：
10.1038/sj.ejhg.5201785
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发表时间：
2007-04-01
影响因子：
5.2
通讯作者：
Devriendt, Koen
中科院分区：
文献类型：
--
作者：
Castermans, Dries;Vermeesch, Joris R.;Devriendt, Koen
自闭症是一种病因和发病机制不明的遗传性神经发育障碍。与自闭症相关的基因的鉴定有望增加我们对其发病机制的了解。罕见情况下，自闭症等神经发育障碍与染色体异常有关。为了确定自闭症的候选基因，我们从携带新染色体异常的特发性自闭症个体开始，启动了一种定位克隆策略。我们报告了一名患有自闭症的男性患者的临床、细胞遗传学和分子发现，该患者没有身体异常，智商正常，携带从头平衡的旁中心倒位 46, XY, inv(10)(q11.1; q21.3)。远端断点破坏了 TRIP8 基因，该基因编码一种蛋白质，预计是与核甲状腺激素受体相关的转录调节因子。然而，迄今为止，尚无甲状腺与自闭症之间联系的报道。此外，同一断点通过位置效应消除了附近基因 REEP3 的表达。受体表达增强蛋白 (REEP) 3 是酵母 Yop1p 的六种人类同源物之一，Yop1p 可能是内质网和高尔基体网络之间细胞囊泡运输的调节因子。这些观察结果表明 TRIP8 和 REEP3 都是自闭症的位置候选基因。此外，我们的数据表明，在研究染色体畸变时选择位置候选基因时，应考虑位置效应。
Autism is a genetic neurodevelopmental disorder of unknown cause and pathogenesis. The identification of genes involved in autism is expected to increase our understanding of its pathogenesis. Infrequently, neurodevelopmental disorders like autism are associated with chromosomal anomalies. To identify candidate genes for autism, we initiated a positional cloning strategy starting from individuals with idiopathic autism carrying a de novo chromosomal anomaly. We report on the clinical, cytogenetic and molecular findings in a male person with autism, no physical abnormalities and normal IQ, carrying a de novo balanced paracentric inversion 46, XY, inv(10)(q11.1; q21.3). The distal breakpoint disrupts the TRIP8 gene, which codes for a protein predicted to be a transcriptional regulator associated with nuclear thyroid hormone receptors. However, no link between thyroid gland and autism has been reported so far. In addition, the same breakpoint abolishes expression of a nearby gene, REEP3, through a position effect. Receptor Expression-Enhancing Proteins (REEP) 3 is one of the six human homologs of yeast Yop1p, a probable regulator of cellular vesicle trafficking between the endoplasmatic reticulum and the Golgi network. These observations suggest that TRIP8 and REEP3 are both positional candidate genes for autism. In addition, our data indicate that in the selection of positional candidate genes when studying chromosomal aberrations, position effects should be taken into account.