Mutation Screening of ADHD

描述（由申请人提供）：注意力缺陷/多动 注意力缺陷多动障碍（ADHD）是一种在儿童早期发病的流行综合征 其特点是注意力不集中，注意力不集中， 和冲动各种研究都证明ADHD与 学业失败，同伴关系不好，家庭功能失调ADHD有 也与受伤，急诊室就诊， 交通违规、烟草、酒精和毒品使用。各种家庭，双胞胎 收养研究表明多动症具有高度遗传性。的 该应用的长期目标是鉴定特定的遗传元件 易患多动症确定这些要素将加强 诊断，并有可能治疗患有这种疾病的儿童。一 各种影像学、神经化学、行为学和药物反应研究 提示前额叶儿茶酚胺通路参与了病因学 ADHD的治疗反应。特别是多巴胺相关的通路 对注意力不集中的问题至关重要。在这项研究中，我们建议筛选75 前额叶皮质发育相关基因，神经元活动依赖 编码区等位基因的能量代谢和儿茶酚胺途径功能 与ADHD亚型相关的变异。作为用于分析的表型，我们 将使用DSM-IV定义的亚型，以及 通过使用潜在类分析。以前确定的群体 儿童将筛查多巴胺通路基因的等位基因变异， 变性高效液相色谱法（DHPLC）。的存在 使用DHPLC鉴定的等位基因变异将通过基因组DNA确认 测序特定等位基因是否与ADHD亚型相关， 使用传递不平衡测试（TDT）进行测试。

DESCRIPTION (provided by the applicant): Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent syndrome with onset in early childhood characterized by problems with attention span, distractibility, hyperactivity and impulsiveness. A variety of studies have documented that ADHD is associated with academic failure, poor peer relationships and family dysfunction. ADHD has also been associated with increases in injuries, visits to emergency rooms, traffic violations, tobacco, alcohol and drug use. A variety of family, twin and adoption studies have demonstrated that ADHD is highly heritable. The long-term goal of this application is to identify specific genetic elements predisposing to ADHD. The identification of such elements would enhance diagnosis and, potentially, the treatment of children with this disorder. A variety of imaging, neurochemical, behavioral and drug response studies implicate pre-frontal catecholamine pathways as being involved in the etiology and treatment response of ADHD. In particular, dopamine-related pathways appear critical to problems with inattention. We propose in this study to screen 75 genes related to pre-frontal cortical development, neuronal activity dependent energy metabolism and catecholamine pathway function for coding region allelic variations associated with subtypes of ADHD. As phenotypes for analysis, we will use both DSM-IV defined subtypes, as well as refined categories derived through the use of latent class analysis. Groups of previously identified children will be screened for allelic variation in dopamine pathway genes using Denaturing High-Performance Liquid Chromatography (DHPLC). The presence of allelic variation identified using DHPLC will be confirmed by genomic DNA sequencing. Whether specific alleles are associated with subtypes of ADHD will be tested using the Transmission Disequilibrium Test (TDT).