CSNK2B splice site mutations in patients cause intellectual disability with or without myoclonic epilepsy. Issue 8 (19th June 2017)

• Record Type: Journal Article
• Authors: Poirier, Karine; Hubert, Laurence; Viot, Géraldine; Rio, Marlène; Billuart, Pierre; Besmond, Claude; Bienvenu, Thierry
• Is Part Of: Human mutation. Volume 38:Issue 8(2017)
• Page Start: 932
• Page End: 941
• Publication Date: 2017-06-19
• Subjects: Caseine kinase 2 -- CSNK2B -- intellectual disability -- splice variants; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.23270
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract : Caseine Kinase 2 (CK2), highly expressed in brain, negatively controls dopamine D1 receptor signaling We identified by exome analysis two de novo likely pathogenic splice variants in the subunit β of CK2 in two unrelated patients with developmental delay and minor facial dysmorphy This study highlight CSNK2B as a new gene for neurodevelopmental disorders Abstract: De novo mutations are a frequent cause of disorders related to brain development. We report the results from the screening of two patients diagnosed with intellectual disability (ID) using exome sequencing to identify new causative de novo mutations. Exome sequencing was conducted in two patient–parent trios to identify de novo variants. In silico and expression studies were also performed to evaluate the functional consequences of these variants. The two patients presented developmental delay with minor facial dysmorphy. One of them presented pharmacoresistant myoclonic epilepsy. We identified two de novo splice variants (c.175+2T>G; c.367+2T>C) in the CSNK2B gene encoding the β subunit of the Caseine kinase 2 (CK2). CK2 is a ubiquitously expressed kinase that is present in high levels in brain and it appears to be constitutively active. The mRNA transcripts were abnormal and significantly reduced in affected fibroblasts and most likely produced truncated proteins. Taking into account that mutations in CSNK2A1, encoding the α subunit of CK2, were previously identified in patients with neurodevelopmental disorders and dysmorphic features, our study confirmed that the protein kinase CK2 plays a major role in brain, and showed that CSNK2, encoding the β subunit, is a novel ID gene. This study adds knowledge to the increasingly growing list of causative and candidate genes in ID and epilepsy, and highlights CSNK2B as a new gene for neurodevelopmental disorders.