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http://purl.uniprot.org/citations/19667227http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19667227http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19667227http://www.w3.org/2000/01/rdf-schema#comment"

Background

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a progressive neurodegenerative disorder associated with thymidine phosphorylase deficiency resulting in high levels of plasma thymidine and a characteristic clinical phenotype.

Objective

To investigate the molecular basis of MNGIE in a patient with a normal plasma thymidine level.

Design

Clinical, neurophysiological, and histopathological examinations as well as molecular and genetic analyses.

Setting

Nerve and muscle center and genetic clinic. Patient A 42-year-old woman with clinical findings strongly suggestive for MNGIE.

Main outcome measures

Clinical description of the disease and its novel genetic cause.

Results

Identification of mitochondrial DNA depletion in muscle samples (approximately 12% of the control mean content) prompted us to look for other causes of our patient's condition. Sequencing of genes associated with mitochondrial DNA depletion-POLG, PEO1, ANT1, SUCLG1, and SUCLA2-did not reveal deleterious mutations. Results of sequencing and array comparative genomic hybridization of the mitochondrial DNA for point mutations and deletions in blood and muscle were negative. Sequencing of RRM2B, a gene encoding cytosolic p53-inducible ribonucleoside reductase small subunit (RIR2B), revealed 2 pathogenic mutations, c.329G>A (p.R110H) and c.362G>A (p.R121H). These mutations are predicted to affect the docking interface of the RIR2B homodimer and likely result in impaired enzyme activity.

Conclusions

This study expands the clinical spectrum of impaired RIR2B function, challenges the notion of locus homogeneity of MNGIE, and sheds light on the pathogenesis of conditions involved in the homeostasis of the mitochondrial nucleotide pool. Our findings suggest that patients with MNGIE who have normal thymidine levels should be tested for RRM2B mutations."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.org/dc/terms/identifier"doi:10.1001/archneurol.2009.139"xsd:string
http://purl.uniprot.org/citations/19667227http://purl.org/dc/terms/identifier"doi:10.1001/archneurol.2009.139"xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Zhang S."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Zhang S."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Shinawi M."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Shinawi M."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Shchelochkov O.A."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Shchelochkov O.A."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Wong L.J."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Wong L.J."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Lichtarge O."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Lichtarge O."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Katsonis P."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Katsonis P."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Shaibani A."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/author"Shaibani A."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/name"Arch. Neurol."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/name"Arch. Neurol."xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/pages"1028-1032"xsd:string
http://purl.uniprot.org/citations/19667227http://purl.uniprot.org/core/pages"1028-1032"xsd:string
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