B. Berti, D. Verrigni, A. Nasca, M. Di Nottia, Daniela Leone, A. Torraco, T. Rizza, E. Bellacchio, A. Legati, C. Palermo, S. Marchet, C. Lamperti, A. Novelli, Eugenio Maria Mercuri, E. Bertini, Marika Pane, Daniele Ghezzi, R. Carrozzo
{"title":"一名患有脑病、心肌病和致命性非癫痫性阵发性难治性呕吐的患者体内的新DNM1L突变","authors":"B. Berti, D. Verrigni, A. Nasca, M. Di Nottia, Daniela Leone, A. Torraco, T. Rizza, E. Bellacchio, A. Legati, C. Palermo, S. Marchet, C. Lamperti, A. Novelli, Eugenio Maria Mercuri, E. Bertini, Marika Pane, Daniele Ghezzi, R. Carrozzo","doi":"10.3390/ijms25147782","DOIUrl":null,"url":null,"abstract":"Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the DNM1L gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy. However, cardiac involvement has been previously reported only in one case. Next-Generation Sequencing (NGS) was used to genetically assess a baby girl characterized by developmental delay with spastic–dystonic, tetraparesis and hypertrophic cardiomyopathy of the left ventricle. Histochemical analysis and spectrophotometric determination of electron transport chain were performed to characterize the muscle biopsy; moreover, the morphology of mitochondria and peroxisomes was evaluated in cultured fibroblasts as well. Herein, we expand the phenotype of DNM1L-related disorder, describing the case of a girl with a heterozygous mutation in DNM1L and affected by progressive infantile encephalopathy, with cardiomyopathy and fatal paroxysmal vomiting correlated with bulbar transitory abnormal T2 hyperintensities and diffusion-weighted imaging (DWI) restriction areas, but without epilepsy. In patients with DNM1L mutations, careful evaluation for cardiac involvement is recommended.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"De Novo DNM1L Mutation in a Patient with Encephalopathy, Cardiomyopathy and Fatal Non-Epileptic Paroxysmal Refractory Vomiting\",\"authors\":\"B. Berti, D. Verrigni, A. Nasca, M. Di Nottia, Daniela Leone, A. Torraco, T. Rizza, E. Bellacchio, A. Legati, C. Palermo, S. Marchet, C. Lamperti, A. Novelli, Eugenio Maria Mercuri, E. Bertini, Marika Pane, Daniele Ghezzi, R. Carrozzo\",\"doi\":\"10.3390/ijms25147782\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the DNM1L gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy. However, cardiac involvement has been previously reported only in one case. Next-Generation Sequencing (NGS) was used to genetically assess a baby girl characterized by developmental delay with spastic–dystonic, tetraparesis and hypertrophic cardiomyopathy of the left ventricle. Histochemical analysis and spectrophotometric determination of electron transport chain were performed to characterize the muscle biopsy; moreover, the morphology of mitochondria and peroxisomes was evaluated in cultured fibroblasts as well. Herein, we expand the phenotype of DNM1L-related disorder, describing the case of a girl with a heterozygous mutation in DNM1L and affected by progressive infantile encephalopathy, with cardiomyopathy and fatal paroxysmal vomiting correlated with bulbar transitory abnormal T2 hyperintensities and diffusion-weighted imaging (DWI) restriction areas, but without epilepsy. 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De Novo DNM1L Mutation in a Patient with Encephalopathy, Cardiomyopathy and Fatal Non-Epileptic Paroxysmal Refractory Vomiting
Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the DNM1L gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy. However, cardiac involvement has been previously reported only in one case. Next-Generation Sequencing (NGS) was used to genetically assess a baby girl characterized by developmental delay with spastic–dystonic, tetraparesis and hypertrophic cardiomyopathy of the left ventricle. Histochemical analysis and spectrophotometric determination of electron transport chain were performed to characterize the muscle biopsy; moreover, the morphology of mitochondria and peroxisomes was evaluated in cultured fibroblasts as well. Herein, we expand the phenotype of DNM1L-related disorder, describing the case of a girl with a heterozygous mutation in DNM1L and affected by progressive infantile encephalopathy, with cardiomyopathy and fatal paroxysmal vomiting correlated with bulbar transitory abnormal T2 hyperintensities and diffusion-weighted imaging (DWI) restriction areas, but without epilepsy. In patients with DNM1L mutations, careful evaluation for cardiac involvement is recommended.
期刊介绍:
The International Journal of Molecular Sciences (ISSN 1422-0067) provides an advanced forum for chemistry, molecular physics (chemical physics and physical chemistry) and molecular biology. It publishes research articles, reviews, communications and short notes. Our aim is to encourage scientists to publish their theoretical and experimental results in as much detail as possible. Therefore, there is no restriction on the length of the papers or the number of electronics supplementary files. For articles with computational results, the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material (including animated pictures, videos, interactive Excel sheets, software executables and others).