Caitlin M Hudac1,2, Joanna Bove3, Shelley Barber4, Michael Duyzend5, Ari Wallace4, Christa Lese Martin6, David H Ledbetter6, Ellen Hanson7, Robin P Goin-Kochel8, LeeAnne Green-Snyder9, Wendy K Chung10,11, Evan E Eichler5, Raphael A Bernier1. 1. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA. 2. Center for Youth Development and Intervention and Department of Psychology at University of Alabama, Tuscaloosa, Alabama, USA. 3. Department of Medicine, University of Washington, Seattle, Washington, USA. 4. Department of School Psychology, University of Washington, Seattle, Washington, USA. 5. Department of Genome Sciences, University of Washington, Seattle, Washington, USA. 6. Autism and Developmental Medicine Institute, Geisinger, Danville, Pennsylvania, USA. 7. Developmental Medicine, Children's Hospital Boston/Harvard Medical School, Boston, Massachusetts, USA. 8. Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. 9. Simons Foundation, New York, New York, USA. 10. Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA. 11. Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
Abstract
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.
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.
Authors: Chandrakanta S Hiremath; Kommu John Vijay Sagar; B K Yamini; Akhila S Girimaji; Raghavendra Kumar; Sanivarapu Lakshmi Sravanti; Hansashree Padmanabha; K N Vykunta Raju; M Thomas Kishore; Preeti Jacob; Jitender Saini; Rose D Bharath; Shekhar P Seshadri; Manoj Kumar Journal: Transl Psychiatry Date: 2021-01-13 Impact factor: 6.222
Authors: Natália Oliva-Teles; Maria Chiara de Stefano; Louise Gallagher; Severin Rakic; Paula Jorge; Goran Cuturilo; Silvana Markovska-Simoska; Isabella Borg; Jeanne Wolstencroft; Zeynep Tümer; Adrian J Harwood; Yllka Kodra; David Skuse Journal: Int J Environ Res Public Health Date: 2020-12-10 Impact factor: 4.614