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

基本信息

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
项目类别：
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

项目摘要

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，能够以前所未有的分辨率识别基因组改变，例如缺失和重复。然而，许多遗传变异已被鉴定出具有未知或不确定的临床意义。新的临床指南建议对患有自闭症谱系障碍 (ASD) 的儿童进行 CMA 测试。自闭症谱系障碍 (ASD) 是最常见的严重发育障碍之一，美国近 1% 的儿童患有自闭症谱系障碍 (ASD)。越来越多的家庭接受检测，并且迫切需要帮助受影响的家庭应对复杂且不确定的检测结果。这项研究将调查接受 CMA 测试的 ASD 儿童父母的心理社会影响，并确定潜在的干预措施，以管理与测试结果及其影响相关的不确定性。检测结果分为三类：（1）阴性，正常； (2) 已知导致病理、异常模式的缺失/重复呈阳性； (3) 不明确，临床意义未知的变异。我们建议采访 60 名经过 CMA 测试的 ASD 儿童家长：其中 20 名儿童家长的结果分别为三类（正常、异常和模糊）。我们将进行开放式、半结构化的电话访谈，并使用扎根理论和内容分析等定性分析方法，分析家长对考试体验和CMA考试结果影响的看法。研究的目的是： (1) 描述家长的测试经历，包括对 CMA 可能提供的内容的期望、对结果的理解、测试结果的感知价值、感知的益处和危害，以及在有关测试的决策中使用结果。儿童的医疗和教育选择； (2) 探讨不确定结果的社会心理影响，以及这些结果是否影响了父母应对自闭症儿童的方式；探索的建构将包括父母的不确定性、压力、耻辱、自责、希望和与孩子状况相关的控制感； (3) 根据结果类型（阴性、阳性或模糊）、社会人口背景以及测试后的时间长度检查相似性和差异。我们将确定经 CMA 测试的自闭症儿童家长认为有效的挑战和应对方法。根据我们的发现，我们将建议医疗服务提供者和家庭采取干预措施，以改善基因检测结果的沟通，解决检测带来的压力，并提出有效的方法来应对与这种新医疗技术相关的不确定性。公共卫生相关性：遗传学技术的进步提高了检测与 ASD 相关的染色体变化的能力，也提高了结果含义的不确定性。鉴于自闭症谱系障碍在美国人口中的患病率很高，研究全基因组检测对自闭症谱系障碍儿童家庭的影响以及为提供者和家长制定循证干预措施具有重要的公共卫生价值。这些干预措施将改善对测试提供的复杂、不确定的遗传信息的理解、沟通和应对。