**1. Introduction**

Leber's hereditary optic neuropathy (LHON) is a form of hereditary disorder caused by pathogenic mutations in mitochondrial DNA. These mutations are non-synonymous, and affect genes coding for different subunits of complex I of the mitochondrial respiratory chain. The occurrence of such kinds of mutations in mtDNA subunits leads to dysfunction of the electron transport, increased reactive oxygen species production, and defective ATP synthesis [1–3]. Retinal ganglion cells are highly susceptible to death during LHON progression, because of their high sensibility to disrupted ATP production and oxidative stress [4]. Therefore, LHON is usually painless, acute, or subacute, central visual loss of one or both eyes, which results in early onset of disability. The onset of Leber's hereditary optic neuropathy is relatively rare and has better visual prognosis. The peak age of onset of visual loss among LHON carriers is 20–30 years old [5]. In some cases, LHON patients have been reported as having

additional neurologic, cardiac, and endocrine disorders [6–8]. Leber's disease is maternally inherited and manifests itself in youth predominantly (~50% of man and ~10% of women). Interestingly, this sex predilection cannot be explained by the principles of mitochondrial inheritance [4].

At the present time, a number of mtDNA point mutations have been described, but the most prevalent are m.3460G>A, m.11778G>A, and m.14484T>C, accounting for about 90% of cases of LHON worldwide. The prevalence of each mutation varies among different populations, but the average is 69–92% for m.11778G>A, and 3–19% for m.14484T>C and m.3460G>A [9–14]. However, there are significant deviations from the average in some populations, for example, among French Canadians 87% of cases are due to m.14484T>C as a result of a founder effect [15]. Moreover, phenotypic expression of these primary mutations has been found to vary in different populations and different pedigrees. This incomplete penetrance suggests that other factors, such as mtDNA haplogroup background, nuclear genetic background, and environmental factors, may influence the modulation of phenotypic expression and severity of the disease [16–18].

Consequently, the worldwide prevalence of LHON varies in different populations and is unknown for the majority of them. This prevalence is estimated to range between 1:30,000 and 1:50,000 [19,20]. The epidemiology of LHON has not been fully investigated in Russian Federation, and our previous studies included the description of isolated cases [21–23]. Hence, in the present study, we report 44 genetically unrelated LHON families, performed whole mtDNA sequencing, and provide molecular genetic data on mutations and the haplogroup background of LHON patients in the Western Siberian population.

#### **2. Materials and Methods**
