Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.
Center for Youth Development and Intervention and Department of Psychology at University of Alabama, Tuscaloosa, Alabama, USA.
Autism Res. 2020 Aug;13(8):1300-1310. doi: 10.1002/aur.2332. Epub 2020 Jun 28.
Individuals with 16p11.2 copy number variant (CNV) show considerable phenotypic heterogeneity. Although autism spectrum disorder (ASD) is reported in approximately 20-23% of individuals with 16p11.2 CNVs, ASD-associated symptoms are observed in those without a clinical ASD diagnosis. Previous work has shown that genetic variation and prenatal and perinatal birth complications influence ASD risk and symptom severity. This study examined the impact of genetic and environmental risk factors on phenotypic heterogeneity among 16p11.2 CNV carriers. Participants included individuals with a 16p11.2 deletion (N = 96) or duplication (N = 77) with exome sequencing from the Simons VIP study. The presence of prenatal factors, perinatal events, additional genetic events, and gender was studied. Regression analyses examined the contribution of each risk factor on ASD symptomatology, cognitive functioning, and adaptive abilities. For deletion carriers, perinatal and additional genetic events were associated with increased ASD symptomatology and decrements in cognitive and adaptive functioning. For duplication carriers, secondary genetic events were associated with greater cognitive impairments. Being female sex was a protective factor for both deletion and duplication carriers. Our findings suggest that ASD-associated risk factors contribute to the variability in symptom presentation in individuals with 16p11.2 CNVs. LAY SUMMARY: There are a wide range of autism spectrum disorder (ASD) symptoms and abilities observed for individuals with genetic changes of the 16p11.2 region. Here, we found perinatal complications contributed to more severe ASD symptoms (deletion carriers) and additional genetic mutations contributed to decreased cognitive abilities (deletion and duplication carriers). A potential protective factor was also observed for females with 16p11.2 variations. Autism Res 2020, 13: 1300-1310. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.
个体携带 16p11.2 拷贝数变异 (CNV) 表现出相当大的表型异质性。虽然大约 20-23%的 16p11.2 CNV 个体患有自闭症谱系障碍 (ASD)，但在没有临床 ASD 诊断的个体中也观察到 ASD 相关症状。先前的工作表明，遗传变异和产前及围产期的出生并发症会影响 ASD 的风险和症状严重程度。本研究检查了遗传和环境风险因素对 16p11.2 CNV 携带者表型异质性的影响。参与者包括来自 Simons VIP 研究的 16p11.2 缺失 (N = 96) 或重复 (N = 77) 的个体的外显子组测序。研究了产前因素、围产期事件、额外的遗传事件和性别。回归分析检查了每个风险因素对 ASD 症状、认知功能和适应能力的贡献。对于缺失携带者，围产期和额外的遗传事件与 ASD 症状增加和认知及适应功能下降有关。对于重复携带者，次要的遗传事件与认知障碍的增加有关。女性性别是缺失和重复携带者的保护因素。我们的研究结果表明，与 ASD 相关的风险因素导致 16p11.2 CNV 个体的症状表现存在差异。
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