The impact of uncertainty in genome-wide testing for Autism Spectrum Disorder

自闭症谱系障碍全基因组测试中不确定性的影响

• 批准号: 8225694
• 负责人: MARIAN F REIFF
• 金额: $ 24万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-09 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8225694
• 关键词: Address; Affect; Age; Autistic Disorder; Categories; Characteristics; Child; Clinical; Communication; Complex; Congenital Abnormality; Counseling; Decision Making; Developmental Delay Disorders; Diagnosis; Diagnostic; Diagnostic tests; Disclosure; Ethnic Origin; Evidence based intervention; Family; Future; Gender; Genetic; Genetic Counseling; Genetic Variation; Genetic screening method; Genome; Genomics; Goals; Guidelines; Health Personnel; High Prevalence; Intellectual functioning disability; Intervention; Interview; Knowledge; Laboratories; Length; Medical; Medical Technology; Microarray Analysis; Motivation; Parenting Education; Parents; Pathology; Patients; Pattern; Perception; Phenotype; Population; Prevalence; Process; Provider; Psychological Impact; Psychosocial Influences; Public Health; Qualitative Methods; Race; Recommendation; Resolution; Resources; Scanning; Social Impacts; Source; Stigmata; Stress; Stress and Coping; Structure; Subgroup; Techniques; Technology; Telephone Interviews; Test Result; Testing; Time; Uncertainty; United States; Variant; autism spectrum disorder; base; clinically significant; coping; developmental disease; exome; expectation; experience; falls; genome sequencing; genome-wide; improved; novel diagnostics; psychosocial; reproductive; satisfaction; social stigma; theories

DESCRIPTION (provided by applicant): Chromosomal Microarray Analysis (CMA) is a genome-wide technology that allows for identification of genomic alterations, such as deletions and duplications, at an unprecedented resolution. However, many genetic variations are identified that have unknown or uncertain clinical significance. New clinical guidelines recommend CMA testing for children with Autism Spectrum Disorder (ASD). ASD is one of the most common serious developmental disorders, found in almost 1% of children in the United States. Increasingly, families are offered testing, and there is an immediate need to help affected families cope with complex and uncertain test results. This study will investigate the psychosocial impact on parents of children with ASD receiving CMA testing, and identify potential interventions for managing the uncertainty associated with the test results and their implications. Test results fall into three categories: (1) Negative, the normal pattern; (2) Positive for a deletion/duplication known to cause pathology, the abnormal pattern; and (3) Ambiguous, a variant of unknown clinical significance. We propose to interview 60 parents of children with ASD who have been tested by CMA: 20 parents of children with results in each of the three categories (normal, abnormal and ambiguous). We will conduct open-ended, semi-structured telephone interviews and use qualitative methods of analysis, including grounded theory and content analysis, to analyze the perspectives of parents regarding the testing experience and impact of CMA test results. The aims of the study are to: (1) Describe parents' experiences of testing, including expectations of what CMA might provide, understanding of results, perceived value of the test results, perceived benefits and harms, and use of results in decisions about the child's medical and educational options; (2) Explore the psychosocial implications of uncertain results, and whether the results have influenced the way parents cope with having a child with ASD; constructs explored will include parental uncertainty, stress, stigma, self-blame, hope, and sense of control in relation to the child's condition; and (3) Examine similarities and differences based on type of result (negative, positive or ambiguous), socio-demographic background, and length of time since testing. We will identify challenges and ways of coping that parents of children with ASD tested by CMA find effective. Based on our findings we will recommend interventions for health providers and families in order to improve communication about genetic test results, address the stressful aspects of testing, and suggest effective ways to deal with the uncertainty associated with this new medical technology. PUBLIC HEALTH RELEVANCE: Technological advances in genetics have increased both the ability to detect chromosomal changes associated with ASD, and the uncertainty surrounding the meaning of results. Given the high prevalence of ASD in the US population, there is significant public health value in studying the impact of genome-wide testing on the families of children with ASD, and developing evidence-based interventions for providers and parents. The interventions would improve understanding, communication and coping with the complex, uncertain genetic information that the test provides.

描述（由申请人提供）：染色体微阵列分析（CMA）是一种全基因组技术，可以以前所未有的分辨率识别基因组改变，例如缺失和重复。但是，鉴定出许多遗传变异，具有未知或不确定的临床意义。新的临床指南建议对自闭症谱系障碍儿童（ASD）进行CMA测试。 ASD是最常见的严重发育障碍之一，在美国近1％的儿童中发现。越来越多地提供家庭测试，并且有必要立即帮助受影响的家庭应对复杂而不确定的测试结果。这项研究将调查对ASD接受CMA测试的儿童父母的心理社会影响，并确定潜在的干预措施来管理与测试结果及其含义相关的不确定性。测试结果分为三类：（1）负，正常模式； （2）已知会导致病理学的缺失/复制阳性，异常模式； （3）模棱两可，是临床意义未知的变体。我们建议采访60名ASD儿童的父母，他们接受了CMA测试：20个孩子的父母在这三个类别中的每一个（正常，异常和模棱两可）中都有结果。我们将进行开放式的，半结构化的电话访谈，并使用定性分析方法，包括扎根的理论和内容分析，以分析父母在CMA测试结果的测试经验和影响方面的观点。该研究的目的是：（1）描述父母的测试经历，包括对CMA可能提供的结果的期望，对结果的理解，测试结果的感知价值，感知的福利和危害以及在有关孩子的医疗和教育方案的决策中使用结果； （2）探索不确定结果的社会心理含义，以及结果是否影响了父母应付生育ASD的方式；探索的结构将包括父母的不确定性，压力，污名，自我塑造，希望和控制感与孩子的状况有关； （3）基于结果的类型（负，正面或模棱两可），社会人口统计学背景以及测试以来的时间长度来检查相似性和差异。我们将确定CMA测试的ASD儿童父母发现有效的挑战和方式。根据我们的发现，我们将建议对健康提供者和家庭进行干预措施，以改善有关基因测试结果的沟通，解决测试的压力方面，并提出有效的方法来处理与这项新医疗技术相关的不确定性。 公共卫生相关性：遗传学的技术进步提高了检测与ASD相关的染色体变化的能力，以及围绕结果含义的不确定性。鉴于ASD在美国人口中的高度流行，研究全基因组测试对ASD儿童家庭的影响以及为提供者和父母开发基于证据的干预措施的公共卫生价值很高。干预措施将改善测试提供的复杂，不确定的遗传信息的理解，交流和应对。