Chuenkongkaew Wanicha Leetiratanai, Chinkulkitnivat Buakhwan, Lertrit Patcharee, Chirapapaisan Niphon, Kaewsutthi Supannee, Suktitipat Bhoom, Mitrpant Chalermchai
Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok10170, Thailand.
Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
World J Clin Cases. 2022 Jul 16;10(20):6944-6953. doi: 10.12998/wjcc.v10.i20.6944.
This study aimed to explore clinical and molecular factors that cause discordance for clinical expression of Leber's hereditary optic neuropathy (LHON) in a pair of identical twins with the 14484 point mutation.
Twin patients with the 14484 point mutation were studied for zygosity by using the Short Tandem Repeats Typing system. For the monozygotic twins, the radioactive restriction and densitometric analyses were used to quantitate the heteroplasmy level for the 14484 point mutation. The mitochondrial genome was analyzed to determine influential factors by mitochondrial deoxyribonucleic acid (DNA) sequencing, denaturing high-performance liquid chromatography and next generation sequencing. For the dizygotic twins, the nuclear DNA was analyzed. The twins with 14484 LHON were monozygotic with homoplasmy. No difference in the point mutation in mitochondrial DNA was found. No modifying genes that potentially influenced the disparity in phenotypic expression of LHON were detected in these twins.
This 11-year follow-up of monozygotic twins showed additional genetic modifications and epigenetic factors are possibly associated with discordance for LHON.
本研究旨在探究在一对携带14484位点突变的同卵双胞胎中，导致Leber遗传性视神经病变（LHON）临床表型不一致的临床和分子因素。
采用短串联重复序列分型系统对携带14484位点突变的双胞胎患者进行同卵性研究。对于同卵双胞胎，使用放射性限制和密度分析来定量14484位点突变的异质性水平。通过线粒体脱氧核糖核酸（DNA）测序、变性高效液相色谱法和下一代测序对线粒体基因组进行分析，以确定影响因素。对于异卵双胞胎，则分析其核DNA。携带14484位点LHON突变的双胞胎为同卵双胞胎且为同质性。线粒体DNA中的点突变未发现差异。在这些双胞胎中未检测到可能影响LHON表型表达差异的修饰基因。
对同卵双胞胎进行的这项为期11年的随访表明，额外的基因修饰和表观遗传因素可能与LHON的不一致性有关。
