青岛大学学报（医学版）2024，Vol.60Issue(2)：184-189,6.DOI:10.11712/jms.2096-5532.2024.60.077
DNM1L基因新变异致EMPF1 1例临床表型和遗传学分析
Clinical phenotype and genetic analysis of a case of EMPF1 caused by a novel DNM1L mutation
摘要
Abstract
Objective To investigate the clinical phenotype and genetic characteristics of encephalopathy due to defective mi-tochondrial and peroxisomal fission 1(EMPF1)caused by a variant in the DNM1L gene.Methods The clinical data and labora-tory findings of a child with EMPF1 were collected.Whole-exome sequencing(WES)was used to detect genetic mutation in the pa-tient and her parents,and the mutation was verified by Sanger dideoxy sequencing.Variant pathogenicity was determined through bioinformatics analysis and multiple amino acid sequence alignment.A three-dimensional(3D)protein structure model was used to model changes in protein structure and intermolecular forces before and after mutation.Results The patient mainly presented with developmental delay,hypotonia,and refractory epilepsy,with symmetrical abnormal signals in bilateral lenticular nuclei and dorsal thalami on magnetic resonance imaging and frequent and persistent myoclonic seizures on video-electroencephalography.WES revealed a de novo heterozygous missense mutation,c.1049G＞C(p.G350A),in the DNM1L gene of the child,and Sanger sequen-cing verified that this mutation was absent in her parents.Multiple amino acid sequence alignment results showed that Gly350 was highly conserved among various species and genera.The 3D protein structure modeling analysis predicted that conformational chan-ges in p.G350A protein would lead to a less stable protein structure,thereby altering protein function.The c.1049G＞C variant was considered likely pathogenic(PS2+PM2+PP2+PP3).Conclusion This case of EMPF1 is caused by c.1049G＞C(p.G350A)mutation in the DNM1L gene.EMPF1 is characterized by psychomotor retardation,limb paralysis,dystonia,and epilepsy,and the combination of clinical phenotyping and genetic testing is helpful for the early diagnosis of EMPF1.关键词
动力蛋白质Ⅰ/线粒体脑肌病/突变,误义/遗传关联研究/基因检测Key words
dynamin Ⅰ/mitochondrial encephalomyopathies/mutation,missense/genetic association studies/genetic tes-ting分类
医药卫生引用本文复制引用
王炳辉,李晶,刘文淼,刘世国,董继承..DNM1L基因新变异致EMPF1 1例临床表型和遗传学分析[J].青岛大学学报（医学版）,2024,60(2):184-189,6.基金项目
国家自然科学基金项目(81371499) （81371499）
青岛市卫计委医药科研指导计划(2016-WJZD067) （2016-WJZD067）
