The discovery of the c.1054C>T; p.R352W mutation in the FOXRED1 gene is a further contribution towards resolving the complex puzzle of the genetic basis of human mitochondrial disease.
Insights into the pathogenic character of a common NUBPL branch-site mutation associated with mitochondrial disease and complex I deficiency using a yeast model.
Distal upper limb myopathy/cachexia is not previously described with dominant POLG mutations and our observations further highlight the diverse clinical spectrum of POLG-related mitochondrial disorders.
Missense mutations in the gene for polymerase gamma 1 (POLG1) cause a number of phenotypically heterogeneous mitochondrial diseases, most commonly progressive external ophthalmoplegia, and are characterized by the accumulation of multiple, large-scale deletions of mitochondrial DNA.
The aim of this study was to determine the prevalence of POLG mutations in an adult population of Australian patients with mitochondrial disease, displaying symptoms commonly associated with POLG-related diseases.
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.
PurposeMutations in POLG, the most common single-gene cause of inherited mitochondrial disease, are diagnostically challenging owing to clinical heterogeneity and overlap between syndromes.
An analysis of the POLG1 gene should be performed for all patients with suspected mitochondrial disease before the introduction of valproate therapy, and treatment with valproic acid should be avoided in these patients.
Our findings suggest that the presence of HOD, in the appropriate clinical setting, should alert the clinician to the possibility of a mitochondrial disorder and the need to screen for mutations in POLG and SURF1 genes.
The combinatorial analyses of mtDNA and POLG revealed a diagnostic yield of 6.7% in patients with suspected mitochondrial disorders but no recognizable syndromes.