Copy number variation in the dosage-sensitive 16p11.2 interval accounts for only a small proportion of autism incidence: a systematic review and meta-analysis
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Purpose Autism is one of the most heritable complex disorders, but the genetic etiology of autism spectrum disorders is unexplained in ∼ 90% of cases. Highly penetrant microdeletions and microduplications of 16p11.2 contribute to the pathogenesis of autism spectrum disorder, but the extent to which these variants account for the total burden of idiopathic autism spectrum disorders has not been systematically investigated.Methods A systematic literature review and meta-analysis were performed to determine the prevalence of these variants among individuals diagnosed with autism spectrum disorders. A planned subgroup analysis was conducted to assess prevalence differences between sporadic and familial autism spectrum disorder cases.Results In the combined analysis of 3613 idiopathic autism spectrum disorder cases from seven studies, the meta-analytic prevalence of these microdeletions and microduplications was 0.76% (95% CI, 0.51-1.12%). When stratified by copy number variant-type, the prevalence of microdeletions was 0.50% (95% CI, 0.31-0.82%) and the prevalence of microduplications was 0.28% (95% CI, 0.14-0.56%). Sporadic autism spectrum disorder cases showed only a slightly higher prevalence than familial cases.Conclusion The number needed to test to identify one such variant is 132 patients (95% CI, 89-198). Such information, especially as it pertains to diagnostic yield in genetic testing, should prove useful to clinicians considering chromosomal microarray analysis in subjects with autism spectrum disorders.
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CHD8 mutation frequency is the highest of all genes screened and nearly matches the frequency of CNVs at 16p11.2, the most frequent recurrent deletion or duplication locus in sporadic ASD.
“The frequency of mutations in this gene is the highest of all genes screened thus far and nearly matches that of CNVs at 16p11.2, which is the most frequent recurrently deleted (0.5%) or duplicated (0.3%) locus in sporadic ASD [50,51].”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [51]
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- Authors
- Walsh, K. M., & Bracken, M. B.
- Affiliations
- Yale University (US)
- ORCID
- Walsh, Kyle M.
- Venue
- Genetics in Medicine
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 13
- Issue
- 5
- Pages
- 377-384
- ISSN
- 1098-3600 (ISSN-L)
- OpenAlex
- W1982282485
- Cited by
- 65
- References
- 41
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 5 · 2018: 1 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 2 · 2012: 6
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Genetics in Medicine (publishedVersion)
- PubMed (publishedVersion)
- 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, copy number variation, 16p11.2, microdeletion, microduplication, genetic etiology, prevalence, chromosomal microarray analysis, genetic testing yield
- MeSH terms
- Child, Child Development Disorders, Pervasive, Chromosome Deletion, Chromosomes, Human, Pair 16, Humans, Incidence, Publication Bias, Gene Dosage, DNA Copy Number Variations, Chromosome Duplication
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