IMPDH2 : a new gene associated with dominant juvenile-onset dystonia-tremor disorder

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http://hdl.handle.net/10138/340504

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Kuukasjärvi , A , Landoni , J C , Kaukonen , J , Juhakoski , M , Auranen , M , Torkkeli , T , Velagapudi , V & Suomalainen , A 2021 , ' IMPDH2 : a new gene associated with dominant juvenile-onset dystonia-tremor disorder ' , European Journal of Human Genetics , vol. 29 , no. 12 , pp. 1833-1837 . https://doi.org/10.1038/s41431-021-00939-1

Title: IMPDH2 : a new gene associated with dominant juvenile-onset dystonia-tremor disorder
Author: Kuukasjärvi, Anna; Landoni, Juan C.; Kaukonen, Jyrki; Juhakoski, Mika; Auranen, Mari; Torkkeli, Tommi; Velagapudi, Vidya; Suomalainen, Anu
Contributor organization: Faculty of Medicine
STEMM - Stem Cells and Metabolism Research Program
University of Helsinki
HUS Neurocenter
Staff Services
Institute for Molecular Medicine Finland
HUSLAB
Department of Neurosciences
Anu Wartiovaara / Principal Investigator
Helsinki Institute of Life Science HiLIFE
Date: 2021-12
Language: eng
Number of pages: 5
Belongs to series: European Journal of Human Genetics
ISSN: 1018-4813
DOI: https://doi.org/10.1038/s41431-021-00939-1
URI: http://hdl.handle.net/10138/340504
Abstract: The aetiology of dystonia disorders is complex, and next-generation sequencing has become a useful tool in elucidating the variable genetic background of these diseases. Here we report a deleterious heterozygous truncating variant in the inosine monophosphate dehydrogenase gene (IMPDH2) by whole-exome sequencing, co-segregating with a dominantly inherited dystonia-tremor disease in a large Finnish family. We show that the defect results in degradation of the gene product, causing IMPDH2 deficiency in patient cells. IMPDH2 is the first and rate-limiting enzyme in the de novo biosynthesis of guanine nucleotides, a dopamine synthetic pathway previously linked to childhood or adolescence-onset dystonia disorders. We report IMPDH2 as a new gene to the dystonia disease entity. The evidence underlines the important link between guanine metabolism, dopamine biosynthesis and dystonia.
Subject: TETRAHYDROBIOPTERIN
BIOSYNTHESIS
METABOLISM
MUTATIONS
1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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