| PRPS1 mutations: four distinct syndromes and potential treatment. | |
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MedLine Citation:
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PMID: 20380929 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phosphoribosylpyrophosphate synthetases (PRSs) catalyze the first step of nucleotide synthesis. Nucleotides are central to cell function, being the building blocks of nucleic acids and serving as cofactors in cellular signaling and metabolism. With this in mind, it is remarkable that mutations in phosphoribosylpyrophosphate synthetase 1 (PRPS1), which is the most ubiquitously expressed gene of the three PRS genes, are compatible with life. Mutations described thus far in PRPS1 are all missense mutations that result in PRS-I superactivity or in variable levels of decreased activity, resulting in X-linked Charcot-Marie-Tooth disease-5 (CMTX5), Arts syndrome, and X-linked nonsyndromic sensorineural deafness (DFN2). Patients with PRS-I superactivity primarily present with uric acid overproduction, mental retardation, ataxia, hypotonia, and hearing impairment. Postlingual progressive hearing loss is found as an isolated feature in DFN2 patients. Patients with CMTX5 and Arts syndrome have peripheral neuropathy, including hearing impairment and optic atrophy. However, patients with Arts syndrome are more severely affected because they also have central neuropathy and an impaired immune system. The neurological phenotype in all four PRPS1-related disorders seems to result primarily from reduced levels of GTP and possibly other purine nucleotides including ATP, suggesting that these disorders belong to the same disease spectrum. Preliminary results of S-adenosylmethionine (SAM) supplementation in two Arts syndrome patients show improvement of their condition, indicating that SAM supplementation in the diet could alleviate some of the symptoms of patients with PRPS1 spectrum diseases by replenishing purine nucleotides (J.C., unpublished data). |
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Authors:
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Arjan P M de Brouwer; Hans van Bokhoven; Sander B Nabuurs; Willem Frans Arts; John Christodoulou; John Duley |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: American journal of human genetics Volume: 86 ISSN: 1537-6605 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-12 Completed Date: 2010-04-22 Revised Date: 2010-10-12 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
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Languages: eng Pagination: 506-18 Citation Subset: IM |
Copyright Information:
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(c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute of Genetic and Metabolic Diseases, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. a.debrouwer@antrg.umcn.nl |
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| MeSH Terms | |
Descriptor/Qualifier:
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Humans Mutation / genetics* Peripheral Nervous System Diseases / genetics*, therapy* Ribose-Phosphate Pyrophosphokinase / genetics* Syndrome |
| Chemical | |
Reg. No./Substance:
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EC 2.7.6.1/PRPS1 protein, human; EC 2.7.6.1/Ribose-Phosphate Pyrophosphokinase |
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