Population prevalence and inheritance pattern of recurrent CNVs associated with neurodevelopmental disorders in 12,252 newborns and their parents
| Autor: | Dinka Smajlagic, Ksenia Lavrichenko, Pål R. Njølstad, Gun Peggy Knudsen, Siren Berland, Marc Vaudel, Stefan Johansson, Per M. Knappskog, Øyvind Helgeland, Jan Haavik, Gunnar Houge |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male DNA Copy Number Variations Population Biology Article 03 medical and health sciences 0302 clinical medicine Gene Frequency mental disorders Gene duplication Genetics Humans Copy-number variation education Allele frequency Genetics (clinical) Sequence Deletion 030304 developmental biology 0303 health sciences education.field_of_study Neurodevelopmental disorders Medical genetics Infant Newborn Inheritance (genetic algorithm) Genomics Penetrance Pedigree Neurodevelopmental delay Female 030217 neurology & neurosurgery Cohort study |
| Zdroj: | European Journal of Human Genetics |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/s41431-020-00707-7 |
| Popis: | Recurrent copy number variations (CNVs) are common causes of neurodevelopmental disorders (NDDs) and associated with a range of psychiatric traits. These CNVs occur at defined genomic regions that are particularly prone to recurrent deletions and duplications and often exhibit variable expressivity and incomplete penetrance. Robust estimates of the population prevalence and inheritance pattern of recurrent CNVs associated with neurodevelopmental disorders (NDD CNVs) are lacking. Here we perform array-based CNV calling in 12,252 mother–father–child trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and analyse the inheritance pattern of 26 recurrent NDD CNVs in 13 genomic regions. We estimate the total prevalence of recurrent NDD CNVs (duplications and deletions) in live-born children to 0.48% (95% C.I.: 0.37–0.62%), i.e., ~1 in 200 newborns has either a deletion or duplication in these NDDs associated regions. Approximately a third of the newborn recurrent NDD CNVs (34%, N = 20/59) are de novo variants. We provide prevalence estimates and inheritance information for each of the 26 NDD CNVs and find higher prevalence than previously reported for 1q21.1 deletions (~1:2000), 15q11.2 duplications (~1:4000), 15q13.3 microdeletions (~1:2500), 16p11.2 proximal microdeletions (~1:2000) and 17q12 deletions (~1:4000) and lower than previously reported prevalence for the 22q11.2 deletion (~1:12,000). In conclusion, our analysis of an unselected and representative population of newborns and their parents provides a clearer picture of the rate of recurrent microdeletions/duplications implicated in neurodevelopmental delay. These results will provide an important resource for genetic diagnostics and counseling. |
| Databáze: | OpenAIRE |
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