**4. Discussion**

#### *4.1. Leber's Hereditary Optic Neuropathy Primary Mutations*

Regarding our preliminary data, the frequencies of primary mutations are different from frequencies reported for Europe and Asia. The most prevalent m.11778G>A (~55%) is less common in Western Siberia than in Europe, at ~69% [9]; as well as in China and Japan, at ~90% [10,13]. The prevalence of m.3460G>A (~24%) is twice as much as in Europe, but m.14484T>C (~14%) do not deviate from those of other European populations [9].

In 12 families with LHON-like manifestation, no known pathogenic mtDNA mutation was found. However, there are other elaborations in which the clinical diagnosis cannot be confirmed by molecular genetic analysis [37,39–41]. Definitively, mtDNA mutation-caused LHON is clinically indistinguishable from the other forms of optic neuropathy, such as a dominant optic neuropathy (DOA), especially when it is sporadic. Compared to LHON, DOA visual loss is detected between ages 4 and 6 in the majority of patients, and 58–84% of patients with DOA report visual impairment by age 11 [42]. In our 12 cases, the ages of onset were between 13–36 years. We will be studying these cases for the mutation spectrum of common pathogenic genes for DOA in future.
