Abstract
Whole exome sequencing (WES) can be used to efficiently identify de novo genetic variants associated with genetically heterogeneous conditions including intellectual disabilities. We have performed WES for 4102 (1847 female; 2255 male) intellectual disability/developmental delay cases and we report five patients with a neurodevelopmental disorder associated with developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and dysmorphic features in whom we have identified de novo missense and canonical splice site mutations in CSNK2A1, the gene encoding CK2α, the catalytic subunit of protein kinase CK2, a ubiquitous serine/threonine kinase composed of two regulatory (β) and two catalytic (α and/or α′) subunits. Somatic mutations in CSNK2A1 have been implicated in various cancers; however, this is the first study to describe a human condition associated with germline mutations in any of the CK2 subunits.
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Acknowledgments
We thank the families for their generous contribution. This work was supported in part by a Grant from the Simons Foundation.
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Megan Cho, Lindsay Henderson, Kyle Retterer, Amy Dameron, Rebecca Willaert, Berivan Baskin, and Jane Juusola are employees of GeneDx. Wendy Chung is a consultant to BioReference Laboratories.
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Data deposition and access: These CSNK2A1 variants have been deposited in ClinVar.
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Okur, V., Cho, M.T., Henderson, L. et al. De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features. Hum Genet 135, 699–705 (2016). https://doi.org/10.1007/s00439-016-1661-y
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DOI: https://doi.org/10.1007/s00439-016-1661-y