Screening of Human LPHN3 for Variants With a Potential Impact on ADHD Susceptibility
Screening of Human LPHN3 for Variants With a Potential Impact on ADHD Susceptibility
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DOI：
10.1002/ajmg.b.31141
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发表时间：
2011-01-01
影响因子：
2.8
通讯作者：
Muenke, Maximilian
中科院分区：
文献类型：
--
作者：
Domene, Sabina;Stanescu, Horia;Muenke, Maximilian
注意缺陷多动障碍（ADHD）是儿童时期最常见的行为障碍，其影响通常会持续到成年。遗传连锁和关联分析的进展已经开始阐明这种复杂疾病的一些遗传因素。最近，我们发现了一种新的ADHD易感基因LPHN3，这是一种位于4q的新型ADHD易感基因，并表明LPHN3常见单倍型可导致ADHD易感性，并预测兴奋剂药物的有效性。在这里，我们对来自美国的139名ADHD患者和52名对照组的LPHN3的整个编码区进行了突变分析。我们确定了21种变异，其中14种已报道，7种是新发现的。这些变化包括5个错义，8个同义和8个内含子变化。有趣的是，无论是易感性还是保护性单倍型等位基因都与显著的编码区改变或典型剪接位点改变无关，这表明决定LPHN3亚型数量和/或质量的非编码变异可能是导致这种常见行为障碍的因素。(C) 2010 Wiley-Liss, Inc。
Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood, and often has effects detectable into adulthood. Advances in genetic linkage and association analysis have begun to elucidate some of the genetic factors underlying this complex disorder. Recently, we identified LPHN3, a novel ADHD susceptibility gene harbored in 4q, and showed that a LPHN3 common haplotype confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Here we present the mutational analysis of the entire coding region of LPHN3 in a cohort of 139 ADHD subjects and 52 controls from across the USA. We identified 21 variants, of which 14 have been reported and 7 are novel. These include 5 missense, 8 synonymous, and 8 intronic changes. Interestingly, neither susceptibility nor protective haplotype alleles are associated with obviously significant coding region changes, or canonical splice site alterations, suggesting that non-coding variations determining the quantity and/or quality of LPHN3 isoforms are the likely contributors to this common behavioral disorder. (C) 2010 Wiley-Liss, Inc.