The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees

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Abstract
Leber hereditary optic neuropathy (LHON) is characterized by acute or subacute bilateral visual loss, and affects mostly young males. The most common mitochondrial DNA mutation responsible for LHON worldwide is G11778A. Despite different genetic backgrounds, which are believed to influence the disease expression, most features of LHON are quite common in different populations. However, there seem to be a few ethnic-specific differences. Analyses of our 30 G11778A LHON pedigrees in Thailand showed some characteristics different from those of Caucasians and Japanese. In particular, our pedigrees showed a lower male to female ratio of affected persons (2.6:1) and much higher prevalence of G11778A blood heteroplasmy (37% of the pedigrees contained at least one heteroplasmic G11778A individual). Heteroplasmicity seemed to influence disease manifestation in our patients but did not appear to alter the onset of the disease. The estimated overall penetrance of our G11778A LHON population was 37% for males and 13% for females. When each of our large pedigrees were considered separately, disease penetration varied from 9 to 45% between the pedigrees, and also varied between different branches of the same large pedigree. Survival analysis showed that the secondary LHON mutations G3316A and C3497T had a synergistic deleterious effect with the G11778A mutation, accelerating the onset of the disease in our patients.