线粒体ND4基因11777C>A突变致Leigh综合征1例家系分析
摘要
目的分析一个线粒体ND4基因11777C>A突变致Leigh综合征家系的资料,探讨其遗传模式。方法收集1例Leigh综合征患儿及其家系的临床资料,并对该Leigh综合征家系进行线粒体DNA测序。结果先证者为7岁余男童,自幼运动和智力发育较同龄儿落后,患儿3岁半出现眼斜视,平时喜静不喜动。肌电图示肌源性损害。头颅MRI示脑干、小脑半球、尾状核异常信号。患儿弟弟现3岁余,已出现眼斜视,头颅MRI异常信号。对该家系患者进行线粒体DNA测序,显示存在线粒体ND4基因11777C>A突变。患儿、患儿弟弟、患儿母亲线粒体ND4基因11777C>A突变率分别为62.36%、67.73%、6.40%。该家系呈母系遗传,目前患儿及患儿弟弟均已发病,患儿母亲尚未有临床表现。结论发现因线粒体ND4基因11777C>A突变所致的Leigh综合征家系,该Leigh综合征家系呈现母系遗传。
引文
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[15] Malfatti EM,Bugiani F,Invernizzi CF,et al.Novel mutations of ND genes in complex Ⅰ deficiency associated with mitochondrial encephalopathy[J].Brain,2007,130(7):1894-1904.
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[18] Hadzsiev K,Maasz A,Kisfali P,et al.Mitochondrial DNA 11777C>A mutation associated leigh syndrome:case report with a review of the previously described pedigrees[J].Neuromol Med,2010,12:277-284.
[19] Bonfante E,Koenig MK,Adejumo RB,et al.The neuroimaging of Leigh syndrome:case series and review of the literature[J].Pediatr Radiol,2016,46(4):443-451.
[20] Hashimoto M,Bacman SR,Peralta S,et al.MitoTALEN:a general approach to reduce mutant mtDNA loads and restore oxidative phosphorylation function in mitochondrial diseases[J].Mol Ther,2015,23(10):1592-1599.
[2] Aretini P,Mazzanti CM,La Ferla M,et al.Next generation sequencing technologies for a successful diagnosis in a cold case of Leigh syndrome[J].BMC Neurol,2018,18(1):99.
[3] Leigh D.Subacute necrotizing encephalomyelopathy in an infant[J].J Neurol Neurosurg Psychiatry,1951,14(3):216-221.
[4] DiMauro S,Schon EA.Mitochondrial respiratory-chain diseases[J].N Engl J Med,2003,348(26):2656-2668.
[5] Sofou K,De Coo IF,Isohanni P,et al.A multicenter study on Leigh syndrome:disease course and predictors of survival[J].Orphanet J Rare Dis,2014,9:52.
[6] Ruhoy IS,Saneto RP.The genetics of leigh syndrome and its im-plications for clinical practice and risk management[J].Appl Clin Genet,2014,7(12):221-234.
[7] 孟庆林,江炜炜.线粒体脑肌病伴高乳酸血症和卒中样发作综合征的临床特点分析[J].临床神经病学杂志,2016,29(4):274-277.
[8] 祝小芬,丁翼,朱筱琦,等.线粒体肌病临床病理学特征及简易乳酸运动实验的筛选价值[J].中国现代神经疾病杂志,2016,16(12):859-864.
[9] Tabarki B,AI-Shafi S,AI-Shawan S,et al.Biotin-responsive basal ganglia disease revisited:clinical,radiologic,and genetic findings[J].Neurology,2013,80(3):261-267.
[10] 吉六舟,李洪涛,孙国运,等.双侧基底节区对称性低密度病变的临床与CT分析[J].中国医学影像学杂志,2008,16(2):127-129.
[11] Luft R,Ikkos D,Palmieri G,et al.A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control:a correlated clinical,biochemical,and morphological study[J].J Clin Invest,1962,41:1776-1804.
[12] Wallace DC,Singh G,Lott MT,et al.Mitochondrial DNA mutation associated with Leber′s hereditary optic neuropath[J].Science,1988,242(4884):1427-1430.
[13] Bourgeron T,Rustin P,Chretien D,et al.Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency[J].Nat Genet,1995,11(2):144-149.
[14] Lee JS,Kim H,Lim BC,et al.Leigh syndrome in childhood:neurologic progression and functional outcome[J].J Clin Neurol,2016,12(2):181-187.
[15] Malfatti EM,Bugiani F,Invernizzi CF,et al.Novel mutations of ND genes in complex Ⅰ deficiency associated with mitochondrial encephalopathy[J].Brain,2007,130(7):1894-1904.
[16] Choi BO,Hwang JH,Kim J,et al.A MELAS syndrome family harboring two mutations in mitochondrial genome[J].Exp Mol Med,2008,40(3):354-360.
[17] 张尧,孙芳,孔庆鹏,等.Leigh综合征患儿核基因和线粒体基因突变的初步分析[J].临床儿科杂志,2008,26(12):1021-1024.
[18] Hadzsiev K,Maasz A,Kisfali P,et al.Mitochondrial DNA 11777C>A mutation associated leigh syndrome:case report with a review of the previously described pedigrees[J].Neuromol Med,2010,12:277-284.
[19] Bonfante E,Koenig MK,Adejumo RB,et al.The neuroimaging of Leigh syndrome:case series and review of the literature[J].Pediatr Radiol,2016,46(4):443-451.
[20] Hashimoto M,Bacman SR,Peralta S,et al.MitoTALEN:a general approach to reduce mutant mtDNA loads and restore oxidative phosphorylation function in mitochondrial diseases[J].Mol Ther,2015,23(10):1592-1599.