Compound heterozygous mutations in electron transfer flavoprotein dehydrogenase identified in a young Chinese woman with late-onset glutaric aciduria type II.
Compound heterozygous mutations in electron transfer flavoprotein dehydrogenase identified in a young Chinese woman with late-onset glutaric aciduria type II.
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一名患有迟发性戊二酸尿症 II 型的年轻中国女性中发现电子转移黄素蛋白脱氢酶的复合杂合突变
DOI：
10.1186/s12944-017-0576-5
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发表时间：
2017-09-26
影响因子：
4.5
通讯作者：
Lu Z
中科院分区：
文献类型：
--
作者：
Xue Y;Zhou Y;Zhang K;Li L;Kayoumu A;Chen L;Wang Y;Lu Z
谷氨酸尿症II型（GA II）是一种影响脂肪酸和氨基酸代谢的常染色体隐性遗传疾病。晚发型GA II疾病几乎完全与电子转移黄素蛋白脱氢酶（ETFDH）基因突变相关。到目前为止，晚发型GA II的临床特征差异很大，给诊断带来了很大的挑战。本研究的目的是描述晚发型GAII患者的临床表型和遗传基础。本研究描述了1例23岁女性迟发性GA II患者的临床和生化表现，并对该家系进行了基因组DNA PCR扩增和ETFDH基因序列分析。我们还使用硅内工具分析突变，并根据美国医学遗传学和基因组学学院（ACMG）提出的标准评估突变的致病性。此病人之肌肉切片检查显示有脂质沉积性肌病。血生化及尿有机酸分析均符合GA Ⅱ。ETFDH基因（NM_004453）的直接序列分析显示复合杂合突变：外显子3上的c.250G > A（p.A84T）和外显子8上的c.920C > G（p.S307C）。根据ACMG标准，这两种突变均被归类为“致病性”。总之，我们的研究描述了晚发型GA II患者的表型和基因型，重申了ETFDH基因筛查在这些患者中的重要性。本文的在线版本（10.1186/s12944-017-0576-5）包含补充材料，可供授权用户使用。
Glutaric aciduria type II (GA II) is an autosomal recessive disorder affecting fatty acid and amino acid metabolism. The late-onset form of GA II disorder is almost exclusively associated with mutations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Till now, the clinical features of late-onset GA II vary widely and pose a great challenge for diagnosis. The aim of the current study is to characterize the clinical phenotypes and genetic basis of a late-onset GAII patient. In this study, we described the clinical and biochemical manifestations of a 23-year-old female Chinese patient with late-onset GA II, and performed genomic DNA-based PCR amplifications and sequence analysis of ETFDH gene of the whole pedigree. We also used in-silicon tools to analyze the mutation and evaluated the pathogenicity of the mutation according to the criteria proposed by American College of Medical Genetics and Genomics (ACMG). The muscle biopsy of this patient revealed lipid storage myopathy. Blood biochemical test and urine organic acid analyses were consistent with GA II. Direct sequence analysis of the ETFDH gene (NM_004453) revealed compound heterozygous mutations: c.250G > A (p.A84T) on exon 3 and c.920C > G (p.S307C) on exon 8. Both mutations were classified as “pathogenic” according to ACMG criteria. In conclusion, our study described the phenotype and genotype of a late-onset GA II patient, reiterating the importance of ETFDH gene screening in these patients. The online version of this article (10.1186/s12944-017-0576-5) contains supplementary material, which is available to authorized users.
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影响因子：
4.2
作者：
Wolfe, Lynne A.;He, Miao;Vockley, Jerry;Payne, Nicole;Rhead, William;Hoppel, Charles;Spector, Elaine;Gernert, Kim;Gibson, K. Michael
通讯作者：
Gibson, K. Michael
影响因子：
14.5
作者：
Olsen, Rikke K. J.;Olpin, Simon E.;Morris, Andrew A. M.
通讯作者：
Morris, Andrew A. M.
影响因子：
4.7
作者：
Wang, Zhi-Qiang;Chen, Xue-Jiao;Wu, Zhi-Ying
通讯作者：
Wu, Zhi-Ying
影响因子：
4.2
作者：
Xi, Jianying;Wen, Bing;Yan, Chuanzhu
通讯作者：
Yan, Chuanzhu
影响因子：
11
作者：
Wen, Bing;Dai, Tingjun;Yan, Chuanzhu
通讯作者：
Yan, Chuanzhu