ArticleAmerican journal of human genetics2005
An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains.
Article in American journal of human genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 129 citations in OpenAlex.
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- Rapid and comprehensive diagnostic method for repeat expansion diseases using nanopore sequencing.NPJ genomic medicine · 2022Article
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- Midbrain atrophy related to parkinsonism in a non-coding repeat expansion disorder: five cases of spinocerebellar ataxia type 31 with nigrostriatal dopaminergic dysfunction.Cerebellum & ataxias · 2021Article
- Repeat-associated non-AUG (RAN) translation: insights from pathology.Laboratory investigation; a journal of technical methods and pathology · 2019Review
- Regulators of Rho GTPases in the Nervous System: Molecular Implication in Axon Guidance and Neurological Disorders.International journal of molecular sciences · 2019Review
- Inter-generational instability of inserted repeats during transmission in spinocerebellar ataxia type 31.Journal of human genetics · 2017Article
- Spontaneous shaker rat mutant - a new model for X-linked tremor/ataxia.Disease models & mechanisms · 2016Article
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- Regulating Rac in the nervous system: molecular function and disease implication of Rac GEFs and GAPs.BioMed research international · 2015Review
- Tyrosine phosphorylation of Dbl regulates GTPase signaling.The Journal of biological chemistry · 2014Article
- Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl.Molecular biology of the cell · 2014Article
- RhoGEFs in cell motility: novel links between Rgnef and focal adhesion kinase.Current molecular medicine · 2014Review
- The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases.Frontiers in cellular neuroscience · 2014Review
- Plekhg4 is a novel Dbl family guanine nucleotide exchange factor protein for rho family GTPases.The Journal of biological chemistry · 2013Article
- Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics.Orphanet journal of rare diseases · 2013Review
- Cellular strategies for regulating functional and nonfunctional protein aggregation.Cell reports · 2012Article
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27 authors at 9 institutions in 1 country.
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Abstract
Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. By positional cloning, we have identified the gene strongly associated with a form of degenerative ataxia (chromosome 16q22.1-linked ADCA) that clinically shows progressive pure cerebellar ataxia. Detailed examination by use of audiogram suggested that sensorineural hearing impairment may be associated with ataxia in our families. After restricting the candidate region in chromosome 16q22.1 by haplotype analysis, we found that all patients from 52 unrelated Japanese families harbor a heterozygous C-->T single-nucleotide substitution, 16 nt upstream of the putative translation initiation site of the gene for a hypothetical protein DKFZP434I216, which we have called "puratrophin-1" (Purkinje cell atrophy associated protein-1). The full-length puratrophin-1 mRNA had an open reading frame of 3,576 nt, predicted to contain important domains, including the spectrin repeat and the guanine-nucleotide exchange factor (GEF) for Rho GTPases, followed by the Dbl-homologous domain, which indicates the role of puratrophin-1 in intracellular signaling and actin dynamics at the Golgi apparatus. Puratrophin-1--normally expressed in a wide range of cells, including epithelial hair cells in the cochlea--was aggregated in Purkinje cells of the chromosome 16q22.1-linked ADCA brains. Consistent with the protein prediction data of puratrophin-1, the Golgi-apparatus membrane protein and spectrin also formed aggregates in Purkinje cells. The present study highlights the importance of the 5' untranslated region (UTR) in identification of genes of human disease, suggests that a single-nucleotide substitution in the 5' UTR could be associated with protein aggregation, and indicates that the GEF protein is associated with cerebellar degeneration in humans.
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