Journal article
Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy.
- Abstract:
- Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 1.6MB, Terms of use)
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- Publisher copy:
- 10.1002/ajmg.c.31791
Authors
- Publisher:
- Wiley
- Journal:
- American Journal of Medical Genetics Part C: Seminars in Medical Genetics More from this journal
- Volume:
- 184
- Issue:
- 2
- Pages:
- 256-266
- Publication date:
- 2020-05-26
- Acceptance date:
- 2020-04-23
- DOI:
- EISSN:
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1552-4876
- ISSN:
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1552-4868
- Pmid:
-
32452638
- Language:
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English
- Keywords:
- Pubs id:
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1107319
- Local pid:
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pubs:1107319
- Deposit date:
-
2020-07-10
Terms of use
- Copyright holder:
- Mountford et al.
- Copyright date:
- 2020
- Rights statement:
- © 2020 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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