Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers
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. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.
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Being female is a protective factor when predicting overall ASD severity in either 16p11.2 CNV.
“In agreement with this, the ratio of males to females with either ASD or ID shows a male predominance in both 16p11.2 CNVs [57], suggesting that being female is a protective factor when predicting overall ASD severity in either 16p11.2 CNV [58].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [58]
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Cites
Standardizing ADOS Scores for a Measure of Severity in Autism Spectrum Disorders
Gotham, K., Pickles, A., & Lord, C. (2009) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-008-0674-3 · Cited by 1,605 · see citing works
A framework for the interpretation of de novo mutation in human disease
Samocha, K. E., Robinson, E. B., Sanders, S. J., Stevens, C., Sabo, A., McGrath, L. M., Kosmicki, J. A., Rehnström, K., Mallick, S., Kirby, A., et al. (2014) · Nature Genetics · doi:10.1038/ng.3050 · Cited by 979 · see citing works
Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
Petrovski, S., Wang, Q., Heinzen, E. L., Allen, A. S., & Goldstein, D. B. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003709 · Cited by 901 · see citing works
Microduplications of 16p11.2 are associated with schizophrenia
Wellcome Trust Case Control Consortium, McCarthy, S. E., Makarov, V., Kirov, G., Addington, A. M., McClellan, J., Yoon, S., Perkins, D. O., Dickel, D. E., Kusenda, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.474 · Cited by 711 · see citing works
A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay
Girirajan, S., Rosenfeld, J. A., Cooper, G. M., Antonacci, F., Siswara, P., Itsara, A., Vives, L., Walsh, T., McCarthy, S. E., Baker, C., et al. (2010) · Nature Genetics · doi:10.1038/ng.534 · Cited by 667 · see citing works
Self-citationDe Novo Mutations in Moderate or Severe Intellectual Disability
Hamdan, F. F., Srour, M., Capo-Chichi, J.-M., Daoud, H., Nassif, C., Patry, L., Massicotte, C., Ambalavanan, A., Spiegelman, D., Diallo, O., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004772 · Cited by 419 · see citing works
Jiang, H.-Y., Xu, L.-L., Shao, L., Xia, R.-M., Yu, Z.-H., Ling, Z.-X., Yang, F., Deng, M., & Ruan, B. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.06.005 · Cited by 391 · see citing works
The Penetrance of Copy Number Variations for Schizophrenia and Developmental Delay
Kirov, G., Rees, E., Walters, J. T. R., Escott-Price, V., Georgieva, L., Richards, A. L., Chambert, K. D., Davies, G., Legge, S. E., Moran, J. L., et al. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.022 · Cited by 368 · see citing works
Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity
Coe, B. P., Stessman, H. A. F., Sulovari, A., Geisheker, M. R., Bakken, T. E., Lake, A. M., Dougherty, J. D., Lein, E. S., Hormozdiari, F., Bernier, R. A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0288-4 · Cited by 330 · see citing works
Self-citationA 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
Zufferey, F., Sherr, E. H., Beckmann, N. D., Hanson, E., Maillard, A. M., Hippolyte, L., Macé, A., Ferrari, C., Kutalik, Z., Andrieux, J., et al. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-101203 · Cited by 326 · see citing works
Self-citationChen, S.-W., Zhong, X.-S., Jiang, L.-N., Zheng, X.-Y., Xiong, Y.-Q., Ma, S.-J., Qiu, M., Huo, S.-T., Ge, J., & Chen, Q. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.08.035 · Cited by 194 · see citing works
Guo, H., Wang, T., Wu, H., Long, M., Coe, B. P., Li, H., Xun, G., Ou, J., Chen, B., Duan, G., et al. (2018) · Molecular Autism · doi:10.1186/s13229-018-0247-z · Cited by 154 · see citing works
Self-citationVisser, J. C., Rommelse, N., Vink, L., Schrieken, M., Oosterling, I. J., van der Gaag, R. J., & Buitelaar, J. K. (2013) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-012-1678-6 · Cited by 50 · cited 1× · see citing works
“…may confer independent risk of ASD symptomatology, be the sequelae of genetic insults, or function interactively with other risk factors [HisleGorman et al., 2018; Chien et al., 2019; Gardener, Spiegelman, & Buka, 2011; Langridge et al., 2013; Matelski & Van de Water, 2016; Visser et al., 2013].”
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16p11.2 Copy Number Variations and Neurodevelopmental Disorders
Rein, B., & Yan, Z. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.09.001 · Cited by 160 · see citing works
- Authors
- Hudac, C. M., Bove, J., Barber, S., Duyzend, M., Wallace, A., Martin, C. L., Ledbetter, D. H., Hanson, E., Goin‐Kochel, R. P., Green‐Snyder, L., Chung, W. K., Eichler, E. E., & Bernier, R. A.
- Affiliations
- University of Alabama (US)
- University of Washington (US)
- Department of School Psychology University of Washington Seattle Washington USA
- Autism & Developmental Medicine Institute (US)
- Boston Children's Hospital (US)
- Baylor College of Medicine (US)
- Simons Foundation (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Hudac, Caitlin M.
- ORCID
- Venue
- Autism Research
- Publisher
- Wiley
- Published
- 2020-06-28
- Volume
- 13
- Issue
- 8
- Pages
- 1300-1310
- ISSN
- 1939-3792 (ISSN-L)
- 1939-3806
- OpenAlex
- W3037492800
- Cited by
- 31
- References
- 13
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 2
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Autism Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Simons Foundation (#198677)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, phenotypic heterogeneity, 16p11.2 deletion, 16p11.2 duplication, perinatal complications, prenatal risk factors, cognitive function, adaptive behavior, sex differences
- MeSH terms
- Autism Spectrum Disorder, Adult, Child, Chromosome Deletion, Chromosomes, Human, Pair 16, Cognition, Female, Heterozygote, Humans, Male, Pregnancy, DNA Copy Number Variations
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