CAJ | 학술논문

目的分析两个Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)家系的临床和分子遗传学特征,阐明LHON的分子机制.方法对两例具有典型LHON临床特征的先证者和家系成员进行眼科学及临床检查.对这2个家系的先证者使用24对有部分重叠的引物进行线粒体DNA全序列扩增分析.结果检查发现这两个家系中视力损害的外显率分别为12.5％、30％.经线粒体全基因组测序分析,在ATPase6编码区发现了未报道过的T8821G同质性变异位点.线粒体全序列分析显示两个家系呈现线粒体DNA多态性,均属于东亚单倍型M10a.T8821G变异位于线粒体ATPase6高度保守性区,编码位于ATPase6第3个跨膜区第99位的丝氨酸,可能导致ATPase6的空间结构发生改变,导致合成ATP的功能受损,最终发生视力损伤.结论线粒体ATPase6 T8821G可能是与LHON相关的致病性线粒体基因变异.
목적 분석량개Leber유전성시신경병변(Leber's hereditary optic neuropathy,LHON)가계적림상화분자유전학특정,천명LHON적분자궤제.방법 대량례구유전형LHON림상특정적선증자화가계성원진행안과학급림상검사.대저2개가계적선증자사용24대유부분중첩적인물진행선립체DNA전서렬확증분석.결과 검사발현저량개가계중시력손해적외현솔분별위12.5％、30％.경선립체전기인조측서분석,재ATPase6편마구발현료미보도과적T8821G동질성변이위점.선립체전서렬분석현시량개가계정현선립체DNA다태성,균속우동아단배형M10a.T8821G변이위우선립체ATPase6고도보수성구,편마위우ATPase6제3개과막구제99위적사안산,가능도치ATPase6적공간결구발생개변,도치합성ATP적공능수손,최종발생시력손상.결론 선립체ATPase6 T8821G가능시여LHON상관적치병성선립체기인변이.
Objective To report on clinical,genetic and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy.Methods Ophthalmological examinations have revealed variable severity and age-at-onset of visual loss among the probands and other matrilineal relatives of both families.The entire mitochondrial genome of the two probands was amplified with PCR in 24 overlapping fragments using sets of oligonucleotide primers.Results The ophthalmological examinations showed that penetrance was 12.5％ and 30.0％ respectively in the two families.Sequence analysis of the complete mitochondrial genomes in these pedigrees has identified unreported homoplasmic T8821G mutation in the ATPase 6 gene and distinct sets of polymorphisms belonging to haplogroups M10a.The T8821G mutation has occurred at the extremely conserved nucleotide (conventional position 99) of the ATPase6.Thus,this mutation may alter structural formation of ATPase6,thereby leading to failure in the synthesis of ATP involved in visual impairment.Conclusion Above observations have suggested that the ATPase6 T8821G mutation may be involved in the pathogenesis of optic neuropathy in these families.