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

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.

SUBMITTER: Kuukasjarvi A

PROVIDER: S-EPMC8633184 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Kuukasjärvi Anna A Landoni Juan C JC Kaukonen Jyrki J Juhakoski Mika M Auranen Mari M Torkkeli Tommi T Velagapudi Vidya V Suomalainen Anu A

European journal of human genetics : EJHG 20210726 12

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 deficien ...[more]

PMID: 34305140

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