Mutation Screening of ADHD

描述(由申请人提供)：注意力缺陷/多动症 精神障碍(ADHD)是一种流行的综合征，起病于儿童早期 以注意力持续时间、注意力不集中、多动症为特征 和冲动。各种研究都证明了ADHD与 学业不及格，同伴关系不佳，家庭功能障碍。多动症有 也与受伤、急诊室就诊的增加有关， 交通违法、吸烟、酗酒和吸毒。各种家庭，双胞胎 收养研究表明，ADHD具有很高的遗传性。这个 这项应用的长期目标是识别特定的遗传元素 易患多动症。查明这类要素将加强 这种疾病的诊断和潜在的治疗。一个 各种成像、神经化学、行为和药物反应研究 额叶前儿茶酚胺通路参与病因学 ADHD的治疗反应。特别是，出现了与多巴胺相关的通路。 对注意力不集中的问题至关重要。我们在这项研究中建议筛选75 与前额叶皮质发育相关的基因，神经元活动依赖 能量代谢和儿茶酚胺途径对编码区等位基因的作用 与ADHD亚型相关的变异。作为分析的表型，我们 将使用DSM-IV定义的子类型以及派生的精细化类别 通过使用潜在类分析。先前确定的组 将对儿童进行多巴胺途径基因的等位基因变异筛查 变性高效液相色谱(DHPLC)。.的存在 用DHPLC鉴定的等位基因变异将被基因组DNA证实 测序。是否特定的等位基因与ADHD的亚型有关 使用传输不平衡测试(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).