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Here we report a deleterious heterozygous truncating variant in the inosine monophosphate dehydrogenase gene (<jats:italic>IMPDH2<\/jats:italic>) 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 <jats:italic>IMPDH2<\/jats:italic> as a new gene to the dystonia disease entity. The evidence underlines the important link between guanine metabolism, dopamine biosynthesis and dystonia.<\/jats:p>","DOI":"10.1038\/s41431-021-00939-1","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T02:02:36Z","timestamp":1627264956000},"page":"1833-1837","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["IMPDH2: a new gene associated with dominant juvenile-onset dystonia-tremor disorder"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-1628","authenticated-orcid":false,"given":"Anna","family":"Kuukasj\u00e4rvi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Landoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyrki","family":"Kaukonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Juhakoski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Auranen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommi","family":"Torkkeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya","family":"Velagapudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-5195","authenticated-orcid":false,"given":"Anu","family":"Suomalainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"939_CR1","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1002\/mds.25475","volume":"28","author":"A Albanese","year":"2013","unstructured":"Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VSC, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord Mov Disord. 2013;28:863\u201373.","journal-title":"Mov Disord Mov Disord"},{"key":"939_CR2","doi-asserted-by":"crossref","unstructured":"Jinnah HA, Sun YV. Dystonia genes and their biological pathways. Neurobiol Dis. 2019;129:159\u201368.","DOI":"10.1016\/j.nbd.2019.05.014"},{"key":"939_CR3","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1146\/annurev.bi.54.070185.003501","volume":"54","author":"CA Nichol","year":"1985","unstructured":"Nichol CA, Smith GK, Duch DS Biosynthesis and metabolism of tetrahydrobiopterin and molybdopterin. Annu Rev Biochem. 1985;54:729\u201364.","journal-title":"Annu Rev Biochem."},{"key":"939_CR4","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/ng1194-236","volume":"8","author":"H Ichinose","year":"1994","unstructured":"Ichinose H, Ohye T, Takahashi E, Seki N, Hori T, Segawa M, et al. 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