title: De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features.
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.
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY, 10032, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Okur
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Cho
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Henderson
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Retterer
authors.affiliation: Carle Physician Group, Urbana, IL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Carle Physician Group, Urbana, IL, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Sattler
authors.affiliation: Ochsner Clinic, New Orleans, LA, USA.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Niyazov
authors.affiliation: Ochsner Clinic, New Orleans, LA, USA.
authors.forename: Meron
authors.initials: M
authors.lastname: Azage
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Smith
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Picker
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Sharyn
authors.initials: S
authors.lastname: Lincoln
authors.affiliation: Department of Pediatrics, McMaster Children's Hospital, Hamilton, ON, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Tarnopolsky
authors.affiliation: Department of Pediatrics, McMaster Children's Hospital, Hamilton, ON, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Brady
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Hans T
authors.initials: HT
authors.lastname: Bjornsson
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Applegate
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Dameron
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Willaert
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Berivan
authors.initials: B
authors.lastname: Baskin
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Juusola
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY, 10032, USA. wkc15@cumc.columbia.edu.|Department of Medicine, Columbia University Medical Center, New York, NY, USA. wkc15@cumc.columbia.edu.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D057215:Body Dysmorphic Disorders / Q000235:genetics* / Q000503:physiopathology; D047390:Casein Kinase II / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D065886:Neurodevelopmental Disorders / Q000235:genetics* / Q000503:physiopathology
chemical_list: C570325:CSNK2A1 protein, human; D047390:Casein Kinase II