1. Hexanucleotide repeat expansion in SCA36 reduces the expression of genes involved in ribosome biosynthesis and protein translation.
- Author
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Morikawa T, Miura S, Uchiyama Y, Hiruki S, Sun Y, Fujioka R, and Shibata H
- Subjects
- Humans, Male, Female, Middle Aged, Nuclear Proteins genetics, Adult, DNA Repeat Expansion genetics, Gene Expression Regulation, Protein Biosynthesis genetics, Ribosomes genetics, Ribosomes metabolism, Spinocerebellar Ataxias genetics, Pedigree
- Abstract
Hereditary spinocerebellar ataxia (SCA) is a group of clinically and genetically heterogeneous inherited disorders characterized by slowly progressive cerebellar ataxia. We ascertained a Japanese pedigree with autosomal dominant SCA comprising four family members, including two patients. We identified a GGCCTG repeat expansion of intron 1 in the NOP56 gene by Southern blotting, resulting in a molecular diagnosis of SCA36. RNA sequencing using peripheral blood revealed that the expression of genes involved in ribosomal organization and translation was decreased in patients carrying the GGCCTG repeat expansion. Genes involved in pathways associated with ribosomal organization and translation were enriched and differentially expressed in the patients. We propose a novel hypothesis that the GGCCTG repeat expansion contributes to the pathogenesis of SCA36 by causing a global disruption of translation resulting from ribosomal dysfunction., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
- Published
- 2024
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