多种酯酰辅酶A脱氢酶缺乏症基因型与表现型关系研究进展
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摘要
多种酯酰辅酶A脱氢酶缺乏症(MADD)是一种脂肪酸、氨基酸及胆固醇代谢障碍的常染色体隐性遗传性疾病。其临床表现多样,可分为3种临床类型。MADD多是由于电子转移黄素蛋白(ETF)或电子转移黄素蛋白脱氢酶(ETFDH)的基因突变而导致的。目前研究发现MADD基因突变谱庞大,异质性强,突变形式复杂。本文主要对MADD基因型与表现型相关性进行综述。
Multiple acyl-coenzyme A dehydrogenase deficiency(MADD) is a kind of autosomal recessive genetic disease which with fatty acids, amino acids and cholesterol metabolism disorder. Its clinical manifestation is diversiform, it can be divided into three clinical types. MADD caused by gene mutations of the electron transfer flavoprotein(ETF) or electron transfer flavoprotein dehydrogenase(ETFDH). Current study found that the gene mutation is heterogeneous and complex. This article mainly discussed the correlation between the genotype and phenotype of MADD.
Multiple acyl-coenzyme A dehydrogenase deficiency(MADD) is a kind of autosomal recessive genetic disease which with fatty acids, amino acids and cholesterol metabolism disorder. Its clinical manifestation is diversiform, it can be divided into three clinical types. MADD caused by gene mutations of the electron transfer flavoprotein(ETF) or electron transfer flavoprotein dehydrogenase(ETFDH). Current study found that the gene mutation is heterogeneous and complex. This article mainly discussed the correlation between the genotype and phenotype of MADD.
引文
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[2]Loehr JP,Goodman SI,Frerman FE.Glutaric acidemia type II:heterogeneity of clinical and biochemical phenotypes[J].Pediatr Res,1990,27(3):311-315.
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[7]Indo Y,Glassberg R,Yokota I,et al.Molecular characterization of variantα-subunit of electron transfer flavoprotein in three patients with glutaric acidemia typeⅡand identification of glycine substitution for valine-157 in the sequence of the precursor,producing an unstable muture protein in a patient[J].Am J Hum Genet,1991,49(3):575-580.
[8]Beard SE,Spector EB,Seltzer WK,et al.Mutations in electron transfer flavoprotein:ubiquinone oxidoreductase(ETF:QO)in glutaric acidemia typeⅡ(GA2)[J].Chin Res,1993,41(1):271A.
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[10]温冰,焉传祝.脂质沉积性肌病的临床、生化、分子病理和药物治疗研究[D].济南:山东大学,2012.
[11]Swanson MA,Usselman RJ,Frerman FE,et al.The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein[J].Biochemistry,2008,47(34):8894-8901.
[12]Usselman RJ,Fielding AJ,Frerman FE,et al.Impact of mutations on the midpoint potential of the[4Fe-4S]+1,+2 cluster and on catalytic activity in electron transfer flavoprotein-ubiquinone oxidoreductase(ETF-QO)[J].Biochemistry,2008,47(1):92-100.
[13]刘鹏,蒲传强.脂质沉积性肌病的临床诊断与基因研究[D].北京:军医进修学院,2008.
[14]Olsen RK,Andresen BS,Christensen E,et al.Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-Co A dehydrogenation deficiency[J].Hum Mutat,2003,22(1):12-23.
[15]Schiff M,Froissart R,Olsen RK,et al.Electron transfer flavoprotein deficiency:functional and molecular aspects[J].Mol Genet Metab,2006,88(2):153-158.
[16]余姗姗,卜碧涛.26例脂质沉积性肌病的临床特点[J].卒中与神经疾病,2014,21(1):36-39.
[17]Laforet P,Vianey-Saban C.Disorders of muscle lipid metabolism:diagnostic and therapeutic challenges[J].Neuromuscul Disord,2010,20(11):693-700.
[18]Grunert SC.Clinical and genetical heterogenity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency[J].Orphanet J Rare Dis,2014,9:117.
[19]Yotsumoto Y,Hasegawa Y,Fukuda S,et al.Clinical and molecular investigations of Japanese cases of glutaric acidemia type 2[J].Mol Genet Metab,2008,94(1),61-67.
[20]Fu HX,Liu XY,Wang ZQ,et al.Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-Co A dehydrogenase deficiency[J].Neurol Sci,2016.
[21]Olsen RK,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-Co A dehydrogenation deficiency[J].Brain,2007,130(Pt 8):2045-2054.
[22]Cornelius N,Frerman FE,Corydon TJ,et al.Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-Co A dehydrogenation deficiency[J].Hum Mol Genet,2012,21(15):3435-3448.
[23]Cotelli MS,Vielmi V,Rimoldi M,et al.Riboflavin-responsive multiple acyl-Co A dehydrogenase deficiency with unknown genetic defect[J].Neurol Sci,2012,33(6):1383-1387.
[24]Bennett MJ.Brown-Vialetto-Van Laere and Fazio Londe syndrome:defects of riboflavin transport with biochemical similarties to multiple acyl-Co A dehyrogenation defects(MADD)[J].J Inherit Metab Dis,2012,35(6):941-942.
[25]毕鸿雁,张芹,赵亚明,等.脂质沉积性肌病临床、病理和基因改变特点分析[J].临床和实验医学杂志,2014,13(9):695-698.
[26]Xi J,Wen B,Lin J,et al.Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-Co A dehydrogenase deficiency[J].J Inherit Metab Dis,2014,37(3):399-404.
[27]Wang ZQ,Chen XJ,Murong SX,et al.Molecular analysis of 51unrelated pedigrees with late-onset multiple acyl-Co A dehydrogenation deficiency(MADD)in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A[J].J Mol Med(Berl),2011,89(6):569-576.
[28]Zhu M,Zhu X,Qi X,et al.Riboflavin-responsive multiple Acyl-Co A dehydrogenation deficiency in 13 cases,and a literature review in mainland Chinese patients[J].J Hum Genet,2014,59(5):256-261.
[29]牛军伟,蒲传强.脂质沉积性肌病的临床、病理与基因学研究[D].北京:中国人民解放军医学院,2015.
[30]Olsen RK,Broner S,Sabaratnam R,et al.The ETFDH c.158A>G variation disrupts the balanced interplay of ESE-and ESS-binding proteins thereby causing missplicing and multiple Acyl-Co A dehydrogenation deficiency[J].Hum Mutat,2014,35(1):86-95.
[2]Loehr JP,Goodman SI,Frerman FE.Glutaric acidemia type II:heterogeneity of clinical and biochemical phenotypes[J].Pediatr Res,1990,27(3):311-315.
[3]Przyrembel H,Wendel U,Becker K,et al.Glutaric aciduria ty Pe ll:report on a previously undescribed metabolic disorder[J].Clin Chim Acta,1976,66(2):227-239.
[4]Finocchiaro G,Ito M,Ikeda Y,et al.Molecular cloning and nucleotide sequence of c DNAs encoding the alpha-subunit of human electron transfer flavoprotein[J].J Biol Chem,1988,263(30):15773-15780.
[5]Finocchiaro G,Colombo I,Garavaglia B,et al.c DNA cloning and mitochondrial import of the beta-subunit of the human electrontransfer flavoprotein[J].Eur J Biochem,1993,213(3):1003-1008.
[6]Goodman SI,Axtell KM,Bindoff LA,et al.Molecular cloning and expression of a c DNA encoding human electron transfer flavoprotein:ubiquinone oxidoreductase[J].Eur J Biochem,1994,219(1/2):277-286.
[7]Indo Y,Glassberg R,Yokota I,et al.Molecular characterization of variantα-subunit of electron transfer flavoprotein in three patients with glutaric acidemia typeⅡand identification of glycine substitution for valine-157 in the sequence of the precursor,producing an unstable muture protein in a patient[J].Am J Hum Genet,1991,49(3):575-580.
[8]Beard SE,Spector EB,Seltzer WK,et al.Mutations in electron transfer flavoprotein:ubiquinone oxidoreductase(ETF:QO)in glutaric acidemia typeⅡ(GA2)[J].Chin Res,1993,41(1):271A.
[9]Colombo I,Finocchiaro G,Garavaglia B,et al.Mutations and polymorphisms of the gene encoding the beta-subunit of the electron transfer flavoprotein in three patients with glutaricacidemia typeⅡ[J].Hum Mol Genet,1994,3(3):429-435.
[10]温冰,焉传祝.脂质沉积性肌病的临床、生化、分子病理和药物治疗研究[D].济南:山东大学,2012.
[11]Swanson MA,Usselman RJ,Frerman FE,et al.The iron-sulfur cluster of electron transfer flavoprotein-ubiquinone oxidoreductase is the electron acceptor for electron transfer flavoprotein[J].Biochemistry,2008,47(34):8894-8901.
[12]Usselman RJ,Fielding AJ,Frerman FE,et al.Impact of mutations on the midpoint potential of the[4Fe-4S]+1,+2 cluster and on catalytic activity in electron transfer flavoprotein-ubiquinone oxidoreductase(ETF-QO)[J].Biochemistry,2008,47(1):92-100.
[13]刘鹏,蒲传强.脂质沉积性肌病的临床诊断与基因研究[D].北京:军医进修学院,2008.
[14]Olsen RK,Andresen BS,Christensen E,et al.Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-Co A dehydrogenation deficiency[J].Hum Mutat,2003,22(1):12-23.
[15]Schiff M,Froissart R,Olsen RK,et al.Electron transfer flavoprotein deficiency:functional and molecular aspects[J].Mol Genet Metab,2006,88(2):153-158.
[16]余姗姗,卜碧涛.26例脂质沉积性肌病的临床特点[J].卒中与神经疾病,2014,21(1):36-39.
[17]Laforet P,Vianey-Saban C.Disorders of muscle lipid metabolism:diagnostic and therapeutic challenges[J].Neuromuscul Disord,2010,20(11):693-700.
[18]Grunert SC.Clinical and genetical heterogenity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency[J].Orphanet J Rare Dis,2014,9:117.
[19]Yotsumoto Y,Hasegawa Y,Fukuda S,et al.Clinical and molecular investigations of Japanese cases of glutaric acidemia type 2[J].Mol Genet Metab,2008,94(1),61-67.
[20]Fu HX,Liu XY,Wang ZQ,et al.Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-Co A dehydrogenase deficiency[J].Neurol Sci,2016.
[21]Olsen RK,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-Co A dehydrogenation deficiency[J].Brain,2007,130(Pt 8):2045-2054.
[22]Cornelius N,Frerman FE,Corydon TJ,et al.Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-Co A dehydrogenation deficiency[J].Hum Mol Genet,2012,21(15):3435-3448.
[23]Cotelli MS,Vielmi V,Rimoldi M,et al.Riboflavin-responsive multiple acyl-Co A dehydrogenase deficiency with unknown genetic defect[J].Neurol Sci,2012,33(6):1383-1387.
[24]Bennett MJ.Brown-Vialetto-Van Laere and Fazio Londe syndrome:defects of riboflavin transport with biochemical similarties to multiple acyl-Co A dehyrogenation defects(MADD)[J].J Inherit Metab Dis,2012,35(6):941-942.
[25]毕鸿雁,张芹,赵亚明,等.脂质沉积性肌病临床、病理和基因改变特点分析[J].临床和实验医学杂志,2014,13(9):695-698.
[26]Xi J,Wen B,Lin J,et al.Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-Co A dehydrogenase deficiency[J].J Inherit Metab Dis,2014,37(3):399-404.
[27]Wang ZQ,Chen XJ,Murong SX,et al.Molecular analysis of 51unrelated pedigrees with late-onset multiple acyl-Co A dehydrogenation deficiency(MADD)in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A[J].J Mol Med(Berl),2011,89(6):569-576.
[28]Zhu M,Zhu X,Qi X,et al.Riboflavin-responsive multiple Acyl-Co A dehydrogenation deficiency in 13 cases,and a literature review in mainland Chinese patients[J].J Hum Genet,2014,59(5):256-261.
[29]牛军伟,蒲传强.脂质沉积性肌病的临床、病理与基因学研究[D].北京:中国人民解放军医学院,2015.
[30]Olsen RK,Broner S,Sabaratnam R,et al.The ETFDH c.158A>G variation disrupts the balanced interplay of ESE-and ESS-binding proteins thereby causing missplicing and multiple Acyl-Co A dehydrogenation deficiency[J].Hum Mutat,2014,35(1):86-95.