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POLG mutations in A ustralian patients with mitochondrial disease
Author(s) -
Woodbridge P.,
Liang C.,
Davis R. L.,
Vandebona H.,
Sue C. M.
Publication year - 2013
Publication title -
internal medicine journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.596
H-Index - 70
eISSN - 1445-5994
pISSN - 1444-0903
DOI - 10.1111/j.1445-5994.2012.02847.x
Subject(s) - medicine , mitochondrial dna , mitochondrial disease , genetics , disease , gene , biology
Background/Aim The nuclear POLG gene encodes the catalytic subunit of DNA polymerase gamma (polγ), the only polymerase involved in the replication and proofreading of mitochondrial DNA . As a consequence, POLG mutations can cause disease through impaired replication of mitochondrial DNA . To date, over 150 different mutations have been identified, with a growing number of associated phenotypes described. The aim of this study was to determine the prevalence of POLG mutations in an adult population of A ustralian patients with mitochondrial disease, displaying symptoms commonly associated with POLG ‐related diseases. Methods The clinical presentations of 322 patients from a specialist adult mitochondrial disease clinic were reviewed. Nineteen exhibited a cluster of three or more predefined clinical manifestations suggestive of POLG ‐related disease: progressive external ophthalmoplegia, seizures and/or an abnormal electroencephalogram, neuropathy, ataxia, liver function abnormalities, migraine or dysphagia/dysarthria. Patients were screened for mutations by direct nucleotide sequencing of the coding and exon‐flanking intronic regions of POLG . Results Five of the 19 patients (26%) displaying a phenotype suggestive of POLG ‐related disease were found to have informative POLG coding mutations ( p.T851A , p.N468D , p.Y831C , p.G517V and novel p.P163S variant). Literature and analysis of these mutations revealed that two of these patients had pathogenic mutations known to cause POLG ‐related disease (patient #1: p.T851A and p.P163S ; patient #2: p.T851A and p.N468D ). Conclusions We conclude that the prevalence of pathogenic POLG mutations in our selected adult A ustralian cohort with suggestive clinical manifestations was 10%. A further 16% of patients had POLG variants but are unlikely to be responsible for causing their disease.