| Molecular diagnosis of Alpers syndrome. | |
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MedLine Citation:
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PMID: 16545482 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Alpers syndrome is a developmental mitochondrial DNA depletion syndrome leading to fatal brain and liver disease in children and young adults. Mutations in the gene for the mitochondrial DNA polymerase (POLG) have recently been shown to cause this disorder. METHODS: The POLG locus was sequenced in 15 sequential probands diagnosed with Alpers syndrome. In addition, the POLG mutations found to cause Alpers syndrome in the 20 cases published to date were analyzed. RESULTS: POLG DNA testing accurately diagnosed 87% (13/15=87%: 95% confidence interval=60-98%) of cases. Five new POLG amino acid substitutions (F749S, R852C, T914P, L966R, and L1173fsX) were found that were associated with Alpers syndrome in five unrelated kindreds, and 14 different allelic combinations of POLG mutations were found to cause Alpers syndrome in the 20 probands published to date. The most common Alpers-causing mutation was the A467T substitution, located in the linker region of the pol gamma protein, which accounted for about 40% of the alleles and was present in 65% of the patients. All patients with POLG mutations had either the A467T or the W748S substitution in the linker region. CONCLUSIONS: Screening for A467T and W748S substitutions in POLG now constitutes the most rapid and sensitive test available for confirming the clinical diagnosis of Alpers syndrome. |
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Authors:
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Khue V Nguyen; Farida S Sharief; Sherine S L Chan; William C Copeland; Robert K Naviaux |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-02-20 |
Journal Detail:
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Title: Journal of hepatology Volume: 45 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-14 Completed Date: 2006-11-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 108-16 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of California, San Diego School of Medicine, 214 Dickinson Street, Bldg. CTF, Rm. C-103, San Diego, CA 92103-8467, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Base Sequence Brain Diseases / genetics Child DNA / chemistry, genetics DNA Primers DNA, Mitochondrial / genetics* DNA-Directed DNA Polymerase / genetics* Diffuse Cerebral Sclerosis of Schilder / diagnosis, enzymology, genetics* Exons Female Humans Liver Diseases / genetics Male Mutation* Pedigree Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/DNA, Mitochondrial; 9007-49-2/DNA; EC 2.7.7.-/POLG protein, human; EC 2.7.7.7/DNA-Directed DNA Polymerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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