核黄素反应性脂质沉积性肌病一家系ETFDH基因突变研究
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摘要
目的探讨核黄素反应性脂质沉积性肌病一家系ETFDH基因的突变方式。方法分析核黄素反应性脂质沉积性肌病家系的临床资料,采用PCR方法对家系中的2例患者、先证者的儿子及孙子以及100名健康对照者的ETFDH基因所有外显子进行DNA测序。结果 2例患者的ETFDH基因第7及10号外显子各发现一个突变,分别是c. 770A> G和c. 1270_1273del;先证者的儿子携带c. 1270_1273del突变。先证者的孙子及100名健康对照者未发现上述突变。结论该c. 1270_1273del突变为新发现的致病性突变,与c. 770A> G突变共同作用导致核黄素反应性脂质沉积性肌病,基因检测有助于明确诊断及提供遗传咨询。
Objective To identify the mutations of ETFDH gene in a riboflavin-responsive lipid storage myopathy family. Methods The clinical data of this riboflavin-responsive lipid storage myopathy family were collected and analyzed.All exons of the ETFDH gene were analyzed by polymerase chain reaction and DNA sequencing in two patients,the son of the proband,the grandson of the proband and 100 unrelated healthy individuals. Results A compound heterozygous mutation which composed of c. 770 A > G and c. 1270_1273 del were identified in this two patients. These two mutations were located in exon 7 and 10 of ETFDH gene respectively. The son of the proband is a carrier of c. 1270_1273 del mutation. Both mutations were not found in the grandson of the proband and the controls. Conclusion The c. 1270_1273 del is a novel disease-causing mutatiion,it together with c. 770 A > G causes riboflavin-responsive lipid storage myopathy. Genetic testing can help to diagnosis and genetic counseling.
Objective To identify the mutations of ETFDH gene in a riboflavin-responsive lipid storage myopathy family. Methods The clinical data of this riboflavin-responsive lipid storage myopathy family were collected and analyzed.All exons of the ETFDH gene were analyzed by polymerase chain reaction and DNA sequencing in two patients,the son of the proband,the grandson of the proband and 100 unrelated healthy individuals. Results A compound heterozygous mutation which composed of c. 770 A > G and c. 1270_1273 del were identified in this two patients. These two mutations were located in exon 7 and 10 of ETFDH gene respectively. The son of the proband is a carrier of c. 1270_1273 del mutation. Both mutations were not found in the grandson of the proband and the controls. Conclusion The c. 1270_1273 del is a novel disease-causing mutatiion,it together with c. 770 A > G causes riboflavin-responsive lipid storage myopathy. Genetic testing can help to diagnosis and genetic counseling.
引文
[1]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.
[2]Wang ZQ,Chen XJ,Murong SX,et al.Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency(MADD)in southern China confirmed the most common ET-FDH mutation and high carrier frequency of c.250G>A[J].J Mol Med,2011,89(6):569-576.
[3]Wen B,Dai T,Li W,et al.Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations[J].J Neurol Neurosurg Psychiatry,2010,81(2):231-236.
[4]Goh LL,Lee YS,Tan ES,et al.Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy:a case report[J].BMC Medical Genomics,2018,11(1):37-45.
[5]王韵,赵丹华,洪道俊,等.核黄素反应性脂质沉积性肌病20个家系的电子转移黄素蛋白脱氢酶基因存在热点突变[J].中华神经科杂志,2011,44(5):309-313.
[6]操基清,张成,李亚勤,等.核黄素反应性脂质沉积性肌病临床特征与基突变分析:两家系3例报告并文献复习[J].中国现代神经疾病杂志,2014,14(6):479-484.
[7]Wen B,Dai T,Li W,et al.Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations[J].J Neurol Neurosurg Psychiatry,2010,81(2):231-236.
[8]Law LK,Tang NL,Hui J,et al.Novel mutations in ETFDH gene in Chinese patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency[J].Clin Chjm Acta,2009,404(2):95-99.
[9]姜涛,熊李,漆学良,等.以横纹肌溶解为表现的脂质沉积性肌病临床、病理与基因改变特点[J].中风与神经疾病杂志,2016,33(1):60-63.
[10]奚剑英,卢家红,赵重波,等.脂质沉积性肌病35例的临床特点及电子转移黄素蛋白脱氢酶基因突变分析[J].中华神经科杂志,2011,44(5):314-321.
[11]Olsen RK,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency[J].Brain,2007,130(8):2045-2054.
[2]Wang ZQ,Chen XJ,Murong SX,et al.Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency(MADD)in southern China confirmed the most common ET-FDH mutation and high carrier frequency of c.250G>A[J].J Mol Med,2011,89(6):569-576.
[3]Wen B,Dai T,Li W,et al.Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations[J].J Neurol Neurosurg Psychiatry,2010,81(2):231-236.
[4]Goh LL,Lee YS,Tan ES,et al.Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy:a case report[J].BMC Medical Genomics,2018,11(1):37-45.
[5]王韵,赵丹华,洪道俊,等.核黄素反应性脂质沉积性肌病20个家系的电子转移黄素蛋白脱氢酶基因存在热点突变[J].中华神经科杂志,2011,44(5):309-313.
[6]操基清,张成,李亚勤,等.核黄素反应性脂质沉积性肌病临床特征与基突变分析:两家系3例报告并文献复习[J].中国现代神经疾病杂志,2014,14(6):479-484.
[7]Wen B,Dai T,Li W,et al.Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations[J].J Neurol Neurosurg Psychiatry,2010,81(2):231-236.
[8]Law LK,Tang NL,Hui J,et al.Novel mutations in ETFDH gene in Chinese patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency[J].Clin Chjm Acta,2009,404(2):95-99.
[9]姜涛,熊李,漆学良,等.以横纹肌溶解为表现的脂质沉积性肌病临床、病理与基因改变特点[J].中风与神经疾病杂志,2016,33(1):60-63.
[10]奚剑英,卢家红,赵重波,等.脂质沉积性肌病35例的临床特点及电子转移黄素蛋白脱氢酶基因突变分析[J].中华神经科杂志,2011,44(5):314-321.
[11]Olsen RK,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency[J].Brain,2007,130(8):2045-2054.