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应用HRM分析Leber遗传性视神经病变家系mtDNA突变 被引量：1

Applying HRM to analysis the mtDNA mutant in a pedigree with Leber's hereditary optic neuropathy
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摘要 目的揭示一个Leber遗传性视神经病变(Leber's hereditary optic neuropathy,LHON)家系的遗传基础。方法对家系成员提取线粒体DNA(mtDNA),直接进行测序分析,用分子克隆法为每个人构建单克隆群,再用高分辨熔解曲线技术和DNA测序的方法,对家系中成员的单克隆群分析统计,计算该家系成员的线粒体DNA突变比例。结果该家系患者mtDNA上11778位核苷酸发生G到A的突变。家系成员中G11778A突变比例分别为:先证者(II2)91.67%;父亲(I2)0%;3位母系家属正常人依次为:(I1)90.83%、(II1)53.16%、(II3)49.16%。结论 G11778A的同质体(即:突变比例达到90%以上)女性仍可不患Leber遗传性视神经病变,该女性后代的平均突变比例远小于先前的报道。 Objective To investigate the genetic basis for a Chinese pedigree with Leber＇s hereditary optic neuropathy （LHON）. Methods Direct DNA sequence was performed for 3 candidate mtDNA sites. High resolution melting and sequencing were carried out to analyse the proportion of mutant mtDNA of each member in the LHON pedigree afterwards. Results A single nucleotide substitution of G for A was found at 11778th of mtDNA. The proportion of mtG11778A for the proband （Ⅱ2）, his father （Ⅰ2）, and three unaffected maternal members （Ⅱ,Ⅲ, Ⅱ3） were 91.67%, 0%, 90.83%, 53.16%, 49.16%, respectively. Conclusion Our study found that the female GI1778A mtDNA mutation carrier Ⅱ, who contains more than 90% G11778A mtDNA mutation, could be unaffected, and her children＇s average proportion of mutant mtDNA was far lower than the previous reports.
作者 万智慧 李修春 段唯 任翔 王擎 刘木根 唐朝晖 李毅
机构地区 华中科技大学人类基因组研究中心
出处 《分子诊断与治疗杂志》 2010年第5期294-298,共5页 Journal of Molecular Diagnostics and Therapy
基金 国家自然科学基金(30771199 30770455)
关键词 LEBER遗传性视神经病变 MTDNA 1 1778位点突变 高分辨熔解曲线分析 测序 Leber＇s hereditary optic neuropathy Point mutation of mtDNA11778 High resolution melting Sequencing
分类号 R774.6 [医药卫生—眼科]
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参考文献15

  • 1Man P Y,Griffiths P G,Brown D T,et al.The epidemiology of Leber hereditary optic neuropathy in the North East of England[J].Am J Hum Genet,2003,72:333-339.
  • 2Spruijt L,Kolbach D N,de Coo R F,et al.Influence of mutation type on clinical expression of Leber hereditary optic neuropathy[J].Am J Ophthalmol,2006,141:676-682.
  • 3Puomila A,Hamalainen P,Kivioja S,et al.Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland[J].Eur J Hum Genet,2007,15:1079-1089.
  • 4Chinnery P F,Andrews R M,Tumbull D M,et al.Leber hereditary optic neuropathy:does heteroplassmy infuence the inheritance and expression of the G11778A mitochondrial DNA mutation[J].Am J Med Genet,2001,98(3):235-243.
  • 5胡慧敏,陈先文.Leber遗传性视神经病的分子遗传学研究进展[J].国际神经病学神经外科学杂志,2006,33(2):136-139. 被引量：2
  • 6Harding A E,Sweeney M G,Govan G G,et al.Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation[J].Am J Hum Genet,1995,57(1):77-86.
  • 7Carelli V,La Morgia C,Iommarini L,et al.Mitochondrial optic neuropathies:how two genomes may kill the same cell type[J].Biosci Rep,2007,27(1-3):173-184.
  • 8Wallace D C,Singh G,Lott M T,et al.Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy[J].Science,1988,242:1427-1430.
  • 9Johns D R,Neufeld M J,Park R D.An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy[J].Biochem Biophys Res Commun,1992,187:1551-1557.
  • 10Howell N,Bindoff L A,McCullough D A,et al.Leber hereditary optic neuropathy:Identification of the same mitochondrial ND1 mutation in six pedigrees[J].Am J Hum Genet,1991,49:939-950.

二级参考文献30

  • 1Leber T. Uber hereditare und congenital-angelegte Sehenervenleiden.Graefe' s Arch Ophthalmol, 1871,17 : 249-291.
  • 2Mackey DA, Oostra RJ, Rosenberg T, et al. Primary pathogenic mtDNA mutations in multigenemtion pedigrees with Leber hereditary optic neuropathy. Am J Hum Genet, 1996, 59:481-485.
  • 3Mashima Y, Yamada K, Wakakura M, et al. Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neumpathy. Curr Eye Res, 1998, 17:403-408.
  • 4Kim JY, Hwang JM, Chang BL, et al. Spectrum of the mitochondrial DNA mutations of Leber' s hereditary optic neuropathy in Koreans. J Neurol,2003, 250:278-281.
  • 5Howell N. Leber hereditary optic neuropathy: mitochondrial mutations and degeneration of the optic nerve. Vision Res, 1997, 37 : 3495-3507.
  • 6Riordan-Eva P, Sanders MD, Govan GG, et cd. The clinical features of fLeber hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain, 1995,118: 319-338.
  • 7May YY, Wang AG, Chang WL, et al. Leber' s hereditary optic neuropathy the spectrum of mitochondrial DNA muta-tions in Chinese patients. Jpn J Ophthalmol, 2002, 46 : 45-51.
  • 8Fauser S, Leo-Kottler B, Bosch D, et al. Confirmation of the 14568 mutation in the mitochondfial ND6 gone as causative in Leber' s hereditary optic neuropathy. Ophthalmic Genct,2002, 23(3): 191-197.
  • 9Chinnery PF, Brown DT, Andrews RM, et al. The mitochondrial ND6 gene is a hot spot for mutations that cause Leber' s hereditary optic neuropathy. Brain, 2001 , 124 ( 1 ) : 209-218.
  • 10Tamopolsky MA, Baker SK, Myint T, et al. Clinical variability in maternally inherited leber hereditary optic neuropathy with the G14459A mutation. Am J Med Genet A, 2004, 124(4): 372-376

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分子诊断与治疗杂志
2010年 第5期

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