De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features

• Published in: Human genetics Vol. 135; no. 7; pp. 699 - 705
• Main Authors: Okur, Volkan, Cho, Megan T., Henderson, Lindsay, Retterer, Kyle, Schneider, Michael, Sattler, Shannon, Niyazov, Dmitriy, Azage, Meron, Smith, Sharon, Picker, Jonathan, Lincoln, Sharyn, Tarnopolsky, Mark, Brady, Lauren, Bjornsson, Hans T., Applegate, Carolyn, Dameron, Amy, Willaert, Rebecca, Baskin, Berivan, Juusola, Jane, Chung, Wendy K.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2016; Springer; Springer Nature B.V
• Subjects: Adolescent; Biomedical and Life Sciences; Biomedicine; Body Dysmorphic Disorders - genetics; Body Dysmorphic Disorders - physiopathology; Casein Kinase II - genetics; Child; Child development; Child, Preschool; Exome - genetics; Female; Gene Function; Gene mutation; Genetic aspects; Genetic Predisposition to Disease; Genomics; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Human Genetics; Humans; Intellectual disabilities; Intellectual Disability - genetics; Intellectual Disability - pathology; Kinases; Metabolic Diseases; Microcephaly; Molecular Medicine; Mutation; Neurodevelopmental Disorders - genetics; Neurodevelopmental Disorders - physiopathology; Original Investigation; Patients; Pediatrics; New York; United States > US; Dysmorphic Feature; Missense Variant; Intellectual Disability; Neurodevelopmental Disorder; Whole Exome Sequencing
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-016-1661-y

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.