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）是童年时期最普遍的传播障碍类型，通常会使个人面临以后的学术困难的风险。尽管SSD的患病率很高，但从小就延伸到青春期/年轻人的SSD的大量纵向研究可以检查残留的言语/语言缺陷以及对教育/职业成就和行为调整的长期后果。本提案是一项为期20年的SSD遗传研究（严重语音疾病的家族研究； NIDCD赠款编号DC000528）的延续，该研究旨在验证已知基因对SSD和合并语言障碍（LI）和阅读障碍（RD）的作用。该项目将利用调查人员组装的SSD家庭的大型家庭数据库，以检查幼儿SSD的长期结果，并使个人面临以后的教育和行为问题最大风险的因素。我们已经检查了275个幼儿SSD的儿童家庭，其中284个儿童到了学龄。在这个项目中，将根据LI，RD和相关的认知技能或与特定染色体区域相关的肠道认知技能或相关认知能力的度量或相关认知能力的度量或成年后重新评估样本。 DNA已由463个同胞配对提供，我们已经对二元和定量性状进行了无模型的遗传连锁分析。我们发现了语音处理与3P12-Q13和6P22-P21.2，语音生产与15q15-Q21的链接的证据，口头短期记忆与1P36的口头短期记忆以及语言技能与1P33-P32。这些连锁研究表明，潜在基因会影响SSD，RD和LI的行为和遗传重叠，我们检验了以下假设：鉴定出患有阅读障碍的神经表达基因也与SSD有关。还将采用适应性功能，社会心理调整和教育/职业成就的措施来检查青春期/年轻成年后SSD早期的功能意义。这些结果将与童年时期的合并存在或不存在有关，在早期时代的持续与SSD的恢复，特定的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。发现将揭示患有早期SDD的个人易受伤害的长期问题的类型，确定风险因素，并确定青少年/年轻成年干预措施的需求，以减少语言和成就方面的核心问题，并确保更有利的教育，职业和行为成果。公共卫生相关性语音障碍（SSD）在儿童中非常普遍，个人和社会成本很高。超过一半的SSD儿童在语言，阅读和拼写方面遇到的学术困难，通常需要其他类型的补救服务，而50％-70％的儿童在12年级的学术困难中表现出一般的学术困难。语言和识字在青少年/年轻人的独立功能中发挥了作用。缺乏这种独立性的个人和社会成本很高。沟通和信息技能和技术在工作场所的重要性将在未来继续增加；因此，患有通讯障碍的个人在这方面将处于不利地位。通过早期识别沟通障碍，建立其原因以及随后的干预，可以增强个人的未来职业成功。拥有SSD史的个人对成年的过渡知之甚少。该项目将提供寿命数据，以确定早期SSD对该人群的后期功能的全部意义，并确定影响青少年/年轻成人结果的因素。