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.
Genes encoding the DNA helicase TWINKLE (C10orf2) or the two subunits of mtDNA polymerase γ (POLγ) (POLG1 and POLG2) have a direct effect on the mitochondrial DNA replication machinery and were reported in many mitochondrial disorders.
Our clustering method provides a powerful tool to predict the pathogenic potential and predicted disease phenotype of novel variants and mutations in POLG, the most common nuclear gene underlying mitochondrial disorders.
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.
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.
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.
Many mutations in POLG, the gene that encodes pol γ, have been associated with mitochondrial diseases such as myocerebrohepatopathy spectrum (MCHS) disorders, Alpers-Huttenlocher syndrome, myoclonic epilepsy myopathy sensory ataxia (MEMSA), ataxia neuropathy spectrum (ANS), and progressive external ophthalmoplegia (PEO).
(1) Mitochondrial disorders(2) are a well-recognized cause; however, to our knowledge this is the first time that such extensive intracranial calcium deposits have been described in a patient with a POLG1 mutation.
Alpers syndrome is one of the most common phenotypes of mitochondrial disorders in early childhood and has been associated with pathogenic mutations in POLG1.
Defects in the mitochondrial DNA replication enzyme, polymerase γ, are an important cause of mitochondrial disease with ∼25% of all adult diagnoses attributed to mutations in the POLG gene.
Sequence analysis of the POLG gene should be considered as a part of routine screening for mitochondrial disorders, even in the absence of apparent mitochondrial DNA abnormalities.
About 150 mutations in the human POLG have been identified in patients with mitochondrial diseases such as Alpers syndrome, progressive external ophthalmoplegia, and ataxia-neuropathy syndromes.
Mutations in the polymerase γ (POLG) gene are among the most common causes of mitochondrial disease and more than 160 POLG mutations have been reported.
We investigated POLG1 in 136 children, all clinically suspected to have mitochondrial disease, with one or more of the following: ataxia, axonal neuropathy, severe epilepsy without known epilepsy syndrome, epileptic encephalopathy, encephalohepatopathy, or neuropathologically verified Alpers syndrome.
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.
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.
Mutations in the DNA polymerase-gamma (POLG) gene are a major cause of clinically heterogeneous mitochondrial diseases, associated with mtDNA depletion and multiple deletions.
POLG, the gene encoding the catalytic subunit of pol gamma, is a major locus for a wide spectrum of mitochondrial diseases with more than 100 known disease mutations.