A Method for Estimating Penetrance of Pathogenic Mutations in a Mitochondrial Genome

Variation in the age of onset is typical of many mitochondrial diseases. The estimation of penetrance of deleterious mtDNA mutations causing such diseases is usually conducted on samples of individuals whose age exceeds the maximum age of the disease manifestation. In the case of rare diseases, samples of sufficient size sometimes cannot be formed. In this study, we propose a method for estimating penetrance involving individuals of any age. The efficiency of the method is demonstrated using Leber hereditary optic neuropathy as an example. It is shown that the method provides an unbiased estimate of penetrance and considerably reduces the error of this estimate in comparison with a sample including individuals whose age exceeds the maximum age of disease manifestation.