A Familial Study of Severe Phonology Disorders

严重音系障碍的家族研究

• 批准号: 8119631
• 负责人: BARBARA A LEWIS
• 金额: $ 63.12万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8119631
• 关键词: 15q14; 15q15; 1p33-p32; 1p34; 1p36; 6p22; 8 year old; Academic achievement; Achievement; Adaptive Behaviors; Adolescence; Adolescent; Adult; Alleles; Awareness; Behavioral; Behavioral Genetics; Candidate Disease Gene; Child; Childhood; Chromosomes; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 7; Clinical Management; Cognitive; Cognitive deficits; Communication; Communication impairment; DNA; Data; Databases; Development; Disadvantaged; Disease; Dyslexia; Early identification; Equation; Exhibits; Family; Future; Genes; Genetic; Genetic Load; Grant; Health; High Prevalence; Impairment; Individual; Intervention; Knowledge; Language; Language Disorders; Life; Link; Longevity; Longitudinal Studies; Measures; Memory; Methods; Modeling; Motor Skills; National Institute on Deafness and Other Communication Disorders; Occupational; Oral; Outcome; Performance; Persons; Phenotype; Play; Population; Problem behavior; Process; Production; Reading; Reading Disorder; Recording of previous events; Recovery; Research; Research Personnel; Residual state; Risk; Risk Factors; Role; Sampling; School-Age Population; Services; Short-Term Memory; Siblings; Social Functioning; Specific qualifier value; Speech; Speech Sound; Symptoms; Technology; Testing; Variant; Vocabulary; Workplace; base; comparison group; cost; density; developmental genetics; early childhood; endophenotype; genetic linkage; genetic linkage analysis; literacy; migration; neurodevelopment; oral motor; phonology; processing speed; psychosocial; psychosocial adjustment; relating to nervous system; skills; spelling; success; trait; young adult

DESCRIPTION (provided by applicant): Speech sound disorders (SSD) are the most prevalent type of communication disorder in early childhood and often place an individual at risk for later academic difficulties. Despite the high prevalence of SSD, there have been no large, longitudinal studies of SSD extending from early childhood into adolescence/young adulthood to examine residual speech/language deficits and long-term consequences for educational/vocational attainment and behavioral adjustment. The present proposal is a continuation of a 20 year genetic study of SSD (A Familial Study of Severe Phonology Disorders; NIDCD grant number DC000528) that seeks to validate the role of known genes for SSD and co-morbid language impairment (LI) and reading disorders (RD). This project will exploit the large database of families with SSD assembled by the investigators to examine long-term outcomes of early childhood SSD and factors that place individuals at greatest risk for later educational and behavioral problems. We have examined 275 families of children with early childhood SSD and followed 284 of these children to school age. In this project, the sample will be reassessed in adolescence/young adulthood on measures of LI, RD, and associated cognitive skills, or endophenotypes that have been linked to specific chromosome regions. DNA has been provided by 463 sibling pairs and we have conducted model-free genetic linkage analysis for binary and quantitative traits. We have found evidence for linkage of phonological processing to 3p12-q13 and 6p22-p21.2, speech sound production to 15q15-q21, verbal short-term memory to 1p36 and language skills to 1p33-p32. These linkage studies suggest that the underlying genes influence the behavioral and genetic overlap of SSD, RD, and LI and we test the hypothesis that neurally expressed genes identified for dyslexia are also associated with SSD. Measures of adaptive functioning, psychosocial adjustment and educational/vocational attainment will also be employed to examine the functional significance of early SSD in adolescence/young adulthood. These outcomes will be related to the presence or absence of co-morbid LI during childhood, persistent vs. recovery of SSD at early school age, specific cognitive deficits, and genetic factors. The interrelationships of these factors will be examined within a structural equation model. Findings will reveal the types of long-term problems to which individuals with early SDD are vulnerable, identify risk factors, and determine needs for adolescent/young adulthood interventions to reduce core problems in language and achievement and insure more favorable educational, vocational, and behavioral outcomes. PUBLIC HEALTH RELEVANCE Speech sound disorders (SSD) are highly prevalent in children and have high personal and societal costs. More than half of children with SSD encounter later academic difficulties in language, reading, and spelling and often require other types of remedial services, with 50%-70% exhibiting general academic difficulty through grade 12. Recent evidence suggests that the residual effects of an early childhood SSD may be life-long. Language and literacy play a role in independent functioning in the adolescent/young adult. Lack of such independence has a high personal and societal cost. The importance of communication and information skills and technologies in the work place will continue to increase in the future; and the individual who has a communication disorder will thus be at a disadvantage in this regard. An individual's future occupational success can be enhanced through the early identification of communication disorders, establishment of their causes, and subsequent intervention. Little is known of the transition into adulthood by the individual with a history of SSD. This project will provide life-span data that is needed to determine full significance of early SSD for the later functioning of this population and identify factors that influence adolescent/young adult outcomes.

描述（由申请人提供）：言语障碍（SSD）是幼儿期最常见的沟通障碍类型，常常使个人面临日后学业困难的风险。尽管 SSD 患病率很高，但还没有针对 SSD 从幼儿期延伸到青春期/青年期的大型纵向研究来检查残余言语/语言缺陷以及对教育/职业成就和行为调整的长期影响。目前的提案是 SSD 20 年基因研究（严重音系障碍的家族研究；NIDCD 拨款号 DC000528）的延续，旨在验证已知基因对 SSD 以及共病语言障碍 (LI) 和阅读的作用疾病（RD）。该项目将利用研究人员收集的 SSD 家庭大型数据库来研究幼儿 SSD 的长期结果以及使个人面临日后教育和行为问题最大风险的因素。我们调查了 275 个患有早期儿童 SSD 儿童的家庭，并对其中 284 名儿童进行了跟踪调查直至学龄。在该项目中，样本将在青春期/青年期重新评估 LI、RD 和相关认知技能，或与特定染色体区域相关的内表型。 DNA 由 463 对兄弟姐妹提供，我们对二元性状和数量性状进行了无模型遗传连锁分析。我们发现了语音处理与 3p12-q13 和 6p22-p21.2 关联、语音产生与 15q15-q21 关联、言语短期记忆与 1p36 关联以及语言技能与 1p33-p32 关联的证据。这些连锁研究表明，潜在的基因影响 SSD、RD 和 LI 的行为和遗传重叠，我们检验了这样的假设：识别为阅读障碍的神经表达基因也与 SSD 相关。适应性功能、心理社会调整和教育/职业成就的测量也将用于检查早期 SSD 在青春期/青年期的功能意义。这些结果将与儿童期是否存在共病 LI、学龄早期 SSD 的持续与恢复、特定认知缺陷和遗传因素有关。这些因素的相互关系将在结构方程模型中进行检查。研究结果将揭示早期 SDD 个体容易遭受的长期问题类型，识别风险因素，并确定青少年/青年期干预的需求，以减少语言和成就方面的核心问题，并确保更有利的教育、职业和行为结果。公共卫生相关性 言语障碍 (SSD) 在儿童中非常普遍，并且会带来高昂的个人和社会成本。超过一半患有 SSD 的儿童在以后会遇到语言、阅读和拼写方面的学业困难，并经常需要其他类型的辅导服务，其中 50%-70% 的儿童在 12 年级时表现出一般的学业困难。最近的证据表明，幼儿时期的SSD可能是终生的。语言和读写能力在青少年/年轻人的独立功能中发挥着重要作用。缺乏这种独立性会带来高昂的个人和社会成本。未来，沟通和信息技能和技术在工作场所的重要性将继续增加；因此，有沟通障碍的人在这方面将处于不利地位。通过早期识别沟通障碍、确定其原因以及随后的干预，可以提高个人未来的职业成功。对于有 SSD 病史的个体如何过渡到成年，我们知之甚少。该项目将提供所需的寿命数据，以确定早期SSD对该人群后期功能的全部意义，并确定影响青少年/年轻人结果的因素。