期刊
JOURNAL OF MEDICAL GENETICS
卷 46, 期 3, 页码 209-214出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jmg.2008.058180
关键词
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资金
- United Mitochondrial Diseases Foundation
- US Army
- Parkinson's Disease Society
- EU [FP6]
- MITOCIRCLE
- Wellcome Trust
- Muscular Dystrophy Campaign
- NHS Trust
- Department of Health
- Medical Research Council [G0601943] Funding Source: researchfish
- MRC [G0601943, G0800674] Funding Source: UKRI
Background: The POLG1 gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA replication and repair. Mutations in POLG1 have been linked to a spectrum of clinical phenotypes, and may account for up to 25% of all adult presentations of mitochondrial disease. Methods and results: We present 14 patients, with characteristic features of mitochondrial disease including progressive external ophthalmoplegia (PEO) and Alpers-Huttenlocher syndrome and laboratory findings indicative of mitochondrial dysfunction, including cytochrome c oxidase (COX) deficiency and multiple deletions or depletion of the mitochondrial DNA. Four novel POLG1 missense substitutions (p.R597W, p.L605R, p.G746S, p.A862T), are described, together with the first adult patient with a recently described polymerase domain mutation (p.R1047W). All novel changes were rare in a control population and affected highly conserved amino acids. Conclusion: The addition of these substitutions including the first report of a dinucleotide mutation (c.1814_1815TT>GC)-to the growing list of defects further confirms the importance of POLG1 mutations as the underlying abnormality in a range of neurological presentations.
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