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A Neurodevelopmental Disorder With Dystonia and Chorea Resulting From Clustering CAMK4 Variants.

Mov Disord. 2020 Nov 19. doi: 10.1002/mds.28398. Epub ahead of print. PMID: 33211350.

Authors/Editors: Zech M, Bardakjian TM, Stoklosa M, Ploski R, Jech R, Gonzalez-Alegre P, Winkelmann J.
Publication Date: 2020

Abstract

Calcium (Ca2+) is a ubiquitous cell-signaling messenger that controls brain function.1 Although disruptions of Ca2+ homeostasis have been reported in a variety of neurodevelopmental and neurodegenerative conditions,2 our knowledge about single-gene disorders caused by mutations in components of the Ca2+-signaling machinery is incomplete. In 2 independent individuals with complex dystonic phenotypes, we recently identified de novo splice-donor variants in the last intron of CAMK4, encoding a key Ca2+- handling protein (calcium/calmodulin-dependent protein kinase-IV [CaMKIV]).3,4 Studies on transcript structure and the gene product revealed that mutation of the donor splice site resulted in a C-terminally truncated form of CaMKIV, lacking its functionally important regulatory domain.3

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