In a screen of 38 individuals with mitochondrial disorders, this variant was found in a familial case from Central Europe. The 58yo father had neuropathy, the proband (26yo female) was compound heterozygous (E1143G) had neuropathy, ataxia and exercise intolerance and the 8yo daughter had epilepsy. Transmission was dominant despite the variant being in the linker region, while most previously reported dominant variants were in the polymerase domain. This variant was not seen in 337 Italians or 301 Finnish, but was seen in 1/336 German controls.
In a screen of 100 children, this mutation was seen in one child with psychomotor retardation, as well as in her healthy father. Since the variant was previously reported to cause different symptoms (ataxia and neuropathy) in a dominant fashion, the authors say this suggests it may be a non-pathogenic polymorphism.
In a screen of 350 patients with phenotypes consistent with POLG-related ataxias, this variant was identified in 5 individuals as the sole mutation and in two individuals as a compound heterozygote in presumptive recessive cases. Controls were only used for the novel mutations. The authors conclude that “it is not clear whether this allele represents a benign polymorphism, or may be contributing to disease by poorly understood mechanisms, which allow it to function either as a dominant or a recessive allele.”
In a screen of 232, 4 unrelated patients were found to carry this variant. However, the inheritance pattern in the families did not support a dominant pattern of inheritance. The authors conclude “the p.G517V should be considered as an unclassified sequence variant for which the clinical relevance is currently unclear”.
In a screen of 26 individuals with ataxias for variants in POLG, this variant was seen in 50f (dx 44yo) with cerebellar ataxia plus external ophthalmoplegia. She was the only individual with this phenotype. Controls for this variant are not mentioned.