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

Anna Kuukasjärvi,Juan C. Landoni, Jyrki Kaukonen, Mika Juhakoski,Mari Auranen, Tommi Torkkeli,Vidya Velagapudi,Anu Suomalainen

EUROPEAN JOURNAL OF HUMAN GENETICS(2021)

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摘要
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.
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关键词
Disease genetics,Movement disorders,Biomedicine,general,Human Genetics,Bioinformatics,Gene Expression,Cytogenetics
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