Affiliations 

  • 1 Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan. mnakashi@hama-med.ac.jp
  • 2 Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Niigata, Japan
  • 3 Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
  • 4 Department of Pediatrics, Yokohama City University Medical Center, Yokohama, Japan
  • 5 Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
  • 6 Department of Pediatrics, Sarawak General Hospital, Sarawak, Malaysia
  • 7 Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • 8 Department of Genome Medicine, National Research Institute for Child Health and Development, Tokyo, Japan
  • 9 Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan
  • 10 Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • 11 Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. naomat@yokohama-cu.ac.jp
J. Hum. Genet., 2019 Apr;64(4):313-322.
PMID: 30655572 DOI: 10.1038/s10038-018-0559-z

Abstract

Casein kinase 2 (CK2) is a serine threonine kinase ubiquitously expressed in eukaryotic cells and involved in various cellular processes. In recent studies, de novo variants in CSNK2A1 and CSNK2B, which encode the subunits of CK2, have been identified in individuals with intellectual disability syndrome. In this study, we describe four patients with neurodevelopmental disorders possessing de novo variants in CSNK2A1 or CSNK2B. Using whole-exome sequencing, we detected two de novo variants in CSNK2A1 in two unrelated Japanese patients, a novel variant c.571C>T, p.(Arg191*) and a recurrent variant c.593A>G, p.(Lys198Arg), and two novel de novo variants in CSNK2B in Japanese and Malaysian patients, c.494A>G, p.(His165Arg) and c.533_534insGT, p.(Pro179Tyrfs*49), respectively. All four patients showed mild to profound intellectual disabilities, developmental delays, and various types of seizures. This and previous studies have found a total of 20 CSNK2A1 variants in 28 individuals with syndromic intellectual disability. The hotspot variant c.593A>G, p.(Lys198Arg) was found in eight of 28 patients. Meanwhile, only five CSNK2B variants were identified in five individuals with neurodevelopmental disorders. We reviewed the previous literature to verify the phenotypic spectrum of CSNK2A1- and CSNK2B-related syndromes.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.