Phasukkijwatana Nopasak, Chuenkongkaew Wanicha L, Suphavilai Rungnapa, Suktitipat Bhoom, Pingsuthiwong Sarinee, Ruangvaravate Ngamkae, Atchaneeyasakul La-Ongsri, Warrasak Sukhuma, Poonyathalang Anuchit, Sura Thanyachai, Lertrit Patcharee
Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
J Hum Genet. 2006;51(4):298-304. doi: 10.1007/s10038-006-0361-1. Epub 2006 Feb 14.
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.
Leber遗传性视神经病变（LHON）的特征是急性或亚急性双侧视力丧失，主要影响年轻男性。在全球范围内，导致LHON的最常见线粒体DNA突变是G11778A。尽管遗传背景不同，人们认为这会影响疾病表现，但LHON的大多数特征在不同人群中相当常见。然而，似乎存在一些特定种族的差异。对我们在泰国的30个G11778A LHON家系的分析显示，有些特征与白种人和日本人不同。特别是，我们的家系显示受影响者的男女比例较低（2.6:1），并且G11778A血液异质性的患病率高得多（37%的家系至少包含一名异质性G11778A个体）。异质性似乎影响了我们患者的疾病表现，但似乎并未改变疾病的发病时间。我们的G11778A LHON人群的估计总体外显率男性为37%，女性为13%。当分别考虑我们的每个大家系时，家系之间的疾病外显率在9%至45%之间变化，并且在同一个大家系的不同分支之间也有所不同。生存分析表明，继发性LHON突变G3316A和C3497T与G11778A突变具有协同有害作用，加速了我们患者疾病的发作。
