Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children.
J Med Genet
; 46(3): 209-14, 2009 Mar.
Article
en En
| MEDLINE
| ID: mdl-19251978
ABSTRACT
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 ANDRESULTS:
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Mitocondriales
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ADN Polimerasa Dirigida por ADN
Tipo de estudio:
Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Revista:
J Med Genet
Año:
2009
Tipo del documento:
Article
País de afiliación:
Reino Unido