Arts syndrome is caused by loss-of-function mutations in PRPS1
| Popis souboru: | application/pdf |
|---|---|
| ISSN: | 0002-9297 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95fb47de2db30beb1d5beb79e865764a https://hdl.handle.net/2066/35095 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....95fb47de2db30beb1d5beb79e865764a |
| Autor: | John A. Duley, Linda S. Weaving, André B.P. van Kuilenburg, Sander B. Nabuurs, Michael Egmont-Petersen, Hans van Bokhoven, Robert A. Ouvrier, Lida Zoetekouw, Melissa Roeffen, Kelly L. Williams, Jennifer A. Donald, Ben C.J. Hamel, Arjan P.M. de Brouwer, Ron A. Wevers, Dorien Lugtenberg, Martijn J.G. Banning, John Christodoulou |
| Přispěvatelé: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Laboratory Genetic Metabolic Diseases |
| Rok vydání: | 2007 |
| Předmět: |
Male
Candidate gene Erythrocytes Genetics and epigenetic pathways of disease [NCMLS 6] Genetic Linkage Protein Conformation Neuroinformatics [DCN 3] medicine.disease_cause chemistry.chemical_compound Perception and Action [DCN 1] Missense mutation Genetics(clinical) Genetics (clinical) Genetics Mutation Phosphoribosyl pyrophosphate Syndrome Hypotonia Pedigree Muscle Hypotonia Female medicine.symptom Functional Neurogenomics [DCN 2] Ataxia Energy and redox metabolism [NCMLS 4] Bioinformatics Mutation Missense Biology Article Cell Line Genomic disorders and inherited multi-system disorders [IGMD 3] Optic Atrophies Hereditary Intellectual Disability Ribose-Phosphate Pyrophosphokinase medicine Humans Hearing Loss Chromosomes Human X Arts syndrome Fibroblasts Glycostation disorders [IGMD 4] Molecular biology Neuromuscular development and genetic disorders [UMCN 3.1] Gene expression profiling chemistry Genetic defects of metabolism [UMCN 5.1] Purines Cellular energy metabolism [UMCN 5.3] |
| Zdroj: | American Journal of Human Genetics, 81, 3, pp. 507-18 American Journal of Human Genetics, 81, 507-18 American journal of human genetics, 81(3), 507-518. Cell Press |
| ISSN: | 0002-9297 |
| Popis: | Contains fulltext : 35096.pdf (Publisher’s version ) (Closed access) Arts syndrome is an X-linked disorder characterized by mental retardation, early-onset hypotonia, ataxia, delayed motor development, hearing impairment, and optic atrophy. Linkage analysis in a Dutch family and an Australian family suggested that the candidate gene maps to Xq22.1-q24. Oligonucleotide microarray expression profiling of fibroblasts from two probands of the Dutch family revealed reduced expression levels of the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1). Subsequent sequencing of PRPS1 led to the identification of two different missense mutations, c.455T-->C (p.L152P) in the Dutch family and c.398A-->C (p.Q133P) in the Australian family. Both mutations result in a loss of phosphoribosyl pyrophosphate synthetase 1 activity, as was shown in silico by molecular modeling and was shown in vitro by phosphoribosyl pyrophosphate synthetase activity assays in erythrocytes and fibroblasts from patients. This is in contrast to the gain-of-function mutations in PRPS1 that were identified previously in PRPS-related gout. The loss-of-function mutations of PRPS1 likely result in impaired purine biosynthesis, which is supported by the undetectable hypoxanthine in urine and the reduced uric acid levels in serum from patients. To replenish low levels of purines, treatment with S-adenosylmethionine theoretically could have therapeutic efficacy, and a clinical trial involving the two affected Australian brothers is currently underway. |
| Databáze: | OpenAIRE |
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