{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:34:49Z","timestamp":1787243689083,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste\u2014Italy","award":["RC 13\/24"],"award-info":[{"award-number":["RC 13\/24"]}]},{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste\u2014Italy","award":["RC 10\/24"],"award-info":[{"award-number":["RC 10\/24"]}]},{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste\u2014Italy","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste\u2014Italy","award":["CUP D93C22000930002"],"award-info":[{"award-number":["CUP D93C22000930002"]}]},{"name":"European Union\u2014NextGenerationEU","award":["RC 13\/24"],"award-info":[{"award-number":["RC 13\/24"]}]},{"name":"European Union\u2014NextGenerationEU","award":["RC 10\/24"],"award-info":[{"award-number":["RC 10\/24"]}]},{"name":"European Union\u2014NextGenerationEU","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"European Union\u2014NextGenerationEU","award":["CUP D93C22000930002"],"award-info":[{"award-number":["CUP D93C22000930002"]}]},{"name":"Italian Ministry of University and Research","award":["RC 13\/24"],"award-info":[{"award-number":["RC 13\/24"]}]},{"name":"Italian Ministry of University and Research","award":["RC 10\/24"],"award-info":[{"award-number":["RC 10\/24"]}]},{"name":"Italian Ministry of University and Research","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Italian Ministry of University and Research","award":["CUP D93C22000930002"],"award-info":[{"award-number":["CUP D93C22000930002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pathogenic variants in DNM1L, encoding dynamin-like protein-1 (DRP1), cause a lethal encephalopathy. DRP1 defective function results in altered mitochondrial networks, characterized by elongated\/spaghetti-like, highly interconnected mitochondria. We validated in yeast the pathogenicity of a de novo DNM1L variant identified by whole exome sequencing performed more than 10 years after the patient\u2019s death. Meanwhile, we reviewed the broadness and specificities of DNM1L-related phenotype. The patient, who exhibited developmental delay in her third year, developed a therapy-refractory myoclonic status epilepticus, followed by neurological deterioration with brain atrophy and refractory epilepsy. She died of heart failure due to hypertrophic cardiomyopathy. She was found to be heterozygous for the DNM1L variant (NM_ 012062.5):c.1201G&gt;A, p.(Gly401Ser). We demonstrated its deleterious impact and dominant negative effect by assessing haploid and diploid mutant yeast strains, oxidative growth, oxygen consumption, frequency of petite, and architecture of the mitochondrial network. Structural modeling of p.(Gly401Ser) predicted the interference of the mutant protein in the self-oligomerization of the DRP1 active complex. DNM1L-related phenotypes include static or (early) lethal encephalopathy and neurodevelopmental disorders. In addition, there may be ophthalmological impairment, peripheral neuropathy, ataxia, dystonia, spasticity, myoclonus, and myopathy. The clinical presentations vary depending on mutations in different DRP1 domains. Few pathogenic variants, the p.(Gly401Ser) included, cause an encephalocardiomyopathy with refractory status epilepticus.<\/jats:p>","DOI":"10.3390\/ijms26020846","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:53:32Z","timestamp":1737442412000},"page":"846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["De Novo DNM1L Pathogenic Variant Associated with Lethal Encephalocardiomyopathy\u2014Case Report and Literature Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5864-5819","authenticated-orcid":false,"given":"Martina","family":"Magistrati","sequence":"first","affiliation":[{"name":"Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze, 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5886-9129","authenticated-orcid":false,"given":"Luisa","family":"Zupin","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell\u2019Istria, 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5090-6028","authenticated-orcid":false,"given":"Eleonora","family":"Lamantea","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-7849","authenticated-orcid":false,"given":"Enrico","family":"Baruffini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze, 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-3766","authenticated-orcid":false,"given":"Daniele","family":"Ghezzi","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, Via F. Sforza, 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8178-6126","authenticated-orcid":false,"given":"Andrea","family":"Legati","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-8463","authenticated-orcid":false,"given":"Fulvio","family":"Celsi","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell\u2019Istria, 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora Maria","family":"Murru","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell\u2019Istria, 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0110-5942","authenticated-orcid":false,"given":"Valeria","family":"Capaci","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell\u2019Istria, 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-9378","authenticated-orcid":false,"given":"Maurizio","family":"Pinamonti","sequence":"additional","affiliation":[{"name":"Institute of Pathological Anatomy and Histology, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Via Giacomo Puccini, 50, 34148 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8241-9726","authenticated-orcid":false,"given":"Rossana","family":"Bussani","sequence":"additional","affiliation":[{"name":"Institute of Pathological Anatomy and Histology, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Via Giacomo Puccini, 50, 34148 Trieste, Italy"},{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste, Via Giacomo Puccini, 50, 34148 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6282-4417","authenticated-orcid":false,"given":"Marco","family":"Carrozzi","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell\u2019Istria, 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4397-9143","authenticated-orcid":false,"given":"Cristina","family":"Dallabona","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze, 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Zeviani","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell\u2019Istria, 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8024-0482","authenticated-orcid":false,"given":"Maria Teresa","family":"Bonati","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofolo, Via dell\u2019Istria, 65, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/humu.23033","article-title":"Biallelic Mutations in DNM1L Are Associated with a Slowly Progressive Infantile Encephalopathy","volume":"37","author":"Nasca","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jpeds.2015.12.060","article-title":"Lethal Disorder of Mitochondrial Fission Caused by Mutations in DNM1L","volume":"171","author":"Yoon","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s10528-017-9829-2","article-title":"DNM1L Variant Alters Baseline Mitochondrial Function and Response to Stress in a Patient with Severe Neurological Dysfunction","volume":"56","author":"Hogarth","year":"2018","journal-title":"Biochem. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1136\/jmg.2004.025502","article-title":"A Third Locus for Dominant Optic Atrophy on Chromosome 22q","volume":"42","author":"Barbet","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1093\/brain\/awx219","article-title":"Mutations in DNM1L, as in OPA1, Result in Dominant Optic Atrophy despite Opposite Effects on Mitochondrial Fusion and Fission","volume":"140","author":"Gerber","year":"2017","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1091\/mbc.12.8.2245","article-title":"Dynamin-Related Protein Drp1 Is Required for Mitochondrial Division in Mammalian Cells","volume":"12","author":"Smirnova","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1749-6632.2010.05629.x","article-title":"Dynamic Regulation of Mitochondrial Fission through Modification of the Dynamin-Related Protein Drp1","volume":"1201","author":"Chang","year":"2010","journal-title":"Ann. New York Acad. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e202101284","DOI":"10.26508\/lsa.202101284","article-title":"Novel DNM1L Variants Impair Mitochondrial Dynamics through Divergent Mechanisms","volume":"5","author":"Nolden","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bernhardt, D., M\u00fcller, M., Reichert, A.S., and Osiewacz, H.D. (2015). Simultaneous Impairment of Mitochondrial Fission and Fusion Reduces Mitophagy and Shortens Replicative Lifespan. Sci. Rep., 5.","DOI":"10.1038\/srep07885"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/humu.23729","article-title":"Clinical-Genetic Features and Peculiar Muscle Histopathology in Infantile DNM1L-Related Mitochondrial Epileptic Encephalopathy","volume":"40","author":"Verrigni","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mito.2015.10.002","article-title":"Validation of a MGM1\/OPA1 Chimeric Gene for Functional Analysis in Yeast of Mutations Associated with Dominant Optic Atrophy","volume":"25","author":"Nolli","year":"2015","journal-title":"Mitochondrion"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1091\/mbc.e02-12-0788","article-title":"Mgm1p, a Dynamin-Related GTPase, Is Essential for Fusion of the Mitochondrial Outer Membrane","volume":"14","author":"Sesaki","year":"2003","journal-title":"Mol. Biol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20150","DOI":"10.1074\/jbc.273.32.20150","article-title":"Fzo1p Is a Mitochondrial Outer Membrane Protein Essential for the Biogenesis of Functional Mitochondria in Saccharomyces Cerevisiae","volume":"273","author":"Rapaport","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/13014","article-title":"The Dynamin-Related GTPase Dnm1 Regulates Mitochondrial Fission in Yeast","volume":"1","author":"Bleazard","year":"1999","journal-title":"Nat. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Boumil, R.M., Letts, V.A., Roberts, M.C., Lenz, C., Mahaffey, C.L., Zhang, Z.-W., Moser, T., and Frankel, W.N. (2010). A Missense Mutation in a Highly Conserved Alternate Exon of Dynamin-1 Causes Epilepsy in Fitful Mice. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001046"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"a003673","DOI":"10.1101\/mcs.a003673","article-title":"De Novo Missense Variant in the GTPase Effector Domain (GED) of DNM1L Leads to Static Encephalopathy and Seizures","volume":"5","author":"Batzir","year":"2019","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1038\/s41431-019-0442-1","article-title":"Increased Diagnostic and New Genes Identification Outcome Using Research Reanalysis of Singleton Exome Sequencing","volume":"27","author":"Bruel","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/cge.13463","article-title":"Effect of Inbreeding on Intellectual Disability Revisited by Trio Sequencing","volume":"95","author":"Kahrizi","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.pediatrneurol.2019.02.017","article-title":"Proband-Only Clinical Exome Sequencing for Neurodevelopmental Disabilities","volume":"99","author":"Kim","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1038\/s41436-019-0518-x","article-title":"Variant Recurrence in Neurodevelopmental Disorders: The Use of Publicly Available Genomic Data Identifies Clinically Relevant Pathogenic Missense Variants","volume":"21","author":"Lecoquierre","year":"2019","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/j.ajhg.2019.11.003","article-title":"Sex-Based Analysis of De Novo Variants in Neurodevelopmental Disorders","volume":"105","author":"Turner","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1136\/jmedgenet-2019-106377","article-title":"Clinical Exome Sequencing as the First-Tier Test for Diagnosing Developmental Disorders Covering Both CNV and SNV: A Chinese Cohort","volume":"57","author":"Dong","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41586-020-2832-5","article-title":"Evidence for 28 Genetic Disorders Discovered by Combining Healthcare and Research Data","volume":"586","author":"Kaplanis","year":"2020","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/cge.13946","article-title":"De Novo Variants in Neurodevelopmental Disorders\u2014Experiences from a Tertiary Care Center","volume":"100","author":"Brunet","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/cge.13951","article-title":"Genetic and Phenotypic Analysis of 101 Patients with Developmental Delay or Intellectual Disability Using Whole-Exome Sequencing","volume":"100","author":"Hiraide","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Halfmeyer, I., Bartolomaeus, T., Popp, B., Radtke, M., Helms, T., Hentschel, J., Popp, D., and Jamra, R.A. (2022). Approach to Cohort-Wide Re-Analysis of Exome Data in 1000 Individuals with Neurodevelopmental Disorders. Genes, 14.","DOI":"10.3390\/genes14010030"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41588-022-01148-2","article-title":"Integrating de Novo and Inherited Variants in 42,607 Autism Cases Identifies Mutations in New Moderate-Risk Genes","volume":"54","author":"Zhou","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103625","DOI":"10.1016\/j.ejmg.2019.01.015","article-title":"De-Novo Mutations in Patients with Chronic Ultra-Refractory Epilepsy with Onset after Age Five Years","volume":"63","author":"McCormack","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.parkreldis.2022.07.003","article-title":"Genetic Overlap between Dystonia and Other Neurologic Disorders: A Study of 1100 Exomes","volume":"102","author":"Dzinovic","year":"2022","journal-title":"Park. Relat. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1001\/jama.2020.26148","article-title":"Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy","volume":"325","author":"Millan","year":"2021","journal-title":"JAMA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ejhg.2016.146","article-title":"Clinical Exome Sequencing: Results from 2819 Samples Reflecting 1000 Families","volume":"25","author":"Trujillano","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1056\/NEJMc1812033","article-title":"Reanalysis of Clinical Exome Sequencing Data","volume":"380","author":"Liu","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100830","DOI":"10.1016\/j.gim.2023.100830","article-title":"Evaluation of an Automated Genome Interpretation Model for Rare Disease Routinely Used in a Clinical Genetic Laboratory","volume":"25","author":"Meng","year":"2023","journal-title":"Genet. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Marouane, A., Neveling, K., Deden, A.C., van den Heuvel, S., Zafeiropoulou, D., Castelein, S., van de Veerdonk, F., Koolen, D.A., Simons, A., and Rodenburg, R. (2023). Lessons Learned from Rapid Exome Sequencing for 575 Critically Ill Patients across the Broad Spectrum of Rare Disease. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1304520"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Barbosa-Gouveia, S., V\u00e1zquez-Mosquera, M.E., Gonz\u00e1lez-Vioque, E., \u00c1lvarez, J.V., Chans, R., Laranjeira, F., Martins, E., Ferreira, A.C., Avila-Alvarez, A., and Couce, M.L. (2021). Utility of Gene Panels for the Diagnosis of Inborn Errors of Metabolism in a Metabolic Reference Center. Genes, 12.","DOI":"10.3390\/genes12081262"},{"key":"ref_37","first-page":"100812","article-title":"The Diagnostic Rate of Inherited Metabolic Disorders by Exome Sequencing in a Cohort of 547 Individuals with Developmental Disorders","volume":"29","author":"Delanne","year":"2021","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e066288","DOI":"10.1136\/bmj-2021-066288","article-title":"Use of Whole Genome Sequencing to Determine Genetic Basis of Suspected Mitochondrial Disorders: Cohort Study","volume":"375","author":"Schon","year":"2021","journal-title":"BMJ"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.pediatrneurol.2022.04.013","article-title":"Phenotype-Genotype Analysis Based on Molecular Classification in 135 Children With Mitochondrial Disease","volume":"132","author":"Wu","year":"2022","journal-title":"Pediatr. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/jimd.12218","article-title":"Mortality of Japanese Patients with Leigh Syndrome: Effects of Age at Onset and Genetic Diagnosis","volume":"43","author":"Ogawa","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/pd.6081","article-title":"Trio Exome Sequencing Is Highly Relevant in Prenatal Diagnostics","volume":"42","author":"Gabriel","year":"2022","journal-title":"Prenat. Diagn."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/pd.6095","article-title":"The Prevalence of Prenatal Sonographic Findings in Postnatal Diagnostic Exome Sequencing Performed for Neurocognitive Phenotypes: A Cohort Study","volume":"42","author":"Perlman","year":"2022","journal-title":"Prenat. Diagn."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Bie, X., Chen, Z., Liu, J., Xie, Z., Li, X., Xiao, M., Zhang, Q., Zhang, Y., and Yang, Y. (2024). A Novel Variant of DNM1L Expanding the Clinical Phenotypic Spectrum: A Case Report and Literature Review. BMC Pediatr., 24.","DOI":"10.1186\/s12887-023-04442-y"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/cge.12805","article-title":"DNM1L-Related Encephalopathy in Infancy with Leigh Syndrome-like Phenotype and Suppression-Burst","volume":"90","author":"Zaha","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3710","DOI":"10.1093\/hmg\/ddy287","article-title":"Aberrant Drp1-Mediated Mitochondrial Division Presents in Humans with Variable Outcomes","volume":"27","author":"Whitley","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/hmg\/ddw059","article-title":"Missense Variants in the Middle Domain of DNM1L in Cases of Infantile Encephalopathy Alter Peroxisomes and Mitochondria When Assayed in Drosophila","volume":"25","author":"Chao","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1056\/NEJMoa064436","article-title":"A Lethal Defect of Mitochondrial and Peroxisomal Fission","volume":"356","author":"Waterham","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/mds.27021","article-title":"Severe Infantile Parkinsonism Because of a de Novo Mutation on DLP1 Mitochondrial-Peroxisomal Protein","volume":"32","author":"Marmiese","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1002\/ajmg.a.61371","article-title":"Novel and Lethal Case of Cardiac Involvement in DNM1L Mitochondrial Encephalopathy","volume":"179","author":"Vandeleur","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1177\/0883073818778203","article-title":"De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-Refractory Myoclonic Status Epilepticus","volume":"33","author":"Ryan","year":"2018","journal-title":"J. Child. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e00961","DOI":"10.1002\/mgg3.961","article-title":"De Novo Pathogenic DNM1L Variant in a Patient Diagnosed with Atypical Hereditary Sensory and Autonomic Neuropathy","volume":"7","author":"Zahir","year":"2019","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Berti, B., Verrigni, D., Nasca, A., Di Nottia, M., Leone, D., Torraco, A., Rizza, T., Bellacchio, E., Legati, A., and Palermo, C. (2024). De Novo DNM1L Mutation in a Patient with Encephalopathy, Cardiomyopathy and Fatal Non-Epileptic Paroxysmal Refractory Vomiting. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147782"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lhuissier, C., Wagner, B.E., Vincent, A., Garraux, G., Hougrand, O., van Coster, R., Benoit, V., Karadurmus, D., Lenaers, G., and Gueguen, N. (2022). Case Report: Thirty-Year Progression of an EMPF1 Encephalopathy Due to Defective Mitochondrial and Peroxisomal Fission Caused by a Novel de Novo Heterozygous DNM1L Variant. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.937885"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104134","DOI":"10.1016\/j.ejmg.2020.104134","article-title":"De Novo DNM1L Variant Presenting with Severe Muscular Atrophy, Dystonia and Sensory Neuropathy","volume":"64","author":"Keller","year":"2021","journal-title":"Eur. J. Med. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wei, Y., and Qian, M. (2021). Case Report: A Novel de Novo Mutation in DNM1L Presenting With Developmental Delay, Ataxia, and Peripheral Neuropathy. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.604105"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1055\/s-0043-1771352","article-title":"DNM1L Variant Presenting as Adolescent-Onset Sensory Neuronopathy, Spasticity, Dystonia, and Ataxia","volume":"21","author":"Wang","year":"2023","journal-title":"J. Pediatr. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Liu, X., Zhang, Z., Li, D., Lei, M., Li, Q., Liu, X., and Zhang, P. (2021). DNM1L-Related Mitochondrial Fission Defects Presenting as Encephalopathy: A Case Report and Literature Review. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.626657"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e258","DOI":"10.1212\/NXG.0000000000000258","article-title":"De Novo DNM1L Mutation Associated with Mitochondrial Epilepsy Syndrome with Fever Sensitivity","volume":"4","author":"Ladds","year":"2018","journal-title":"Neurol. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1055\/s-0039-1685217","article-title":"A De Novo Dominant Negative Mutation in DNM1L Causes Sudden Onset Status Epilepticus with Subsequent Epileptic Encephalopathy","volume":"50","author":"Schmid","year":"2019","journal-title":"Neuropediatrics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1002\/ajmg.a.37721","article-title":"A Novel de Novo Dominant Negative Mutation in DNM1L Impairs Mitochondrial Fission and Presents as Childhood Epileptic Encephalopathy","volume":"170","author":"Fahrner","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1684\/epd.2019.1036","article-title":"A Rasmussen Encephalitis, Autoimmune Encephalitis, and Mitochondrial Disease Mimicker: Expanding the DNM1L-Associated Intractable Epilepsy and Encephalopathy Phenotype","volume":"21","author":"Nolan","year":"2019","journal-title":"Epileptic Disord."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e14879","DOI":"10.1111\/ped.14879","article-title":"Severe Metabolic Acidosis with Cardiac Involvement in DNM1L-Related Mitochondrial Encephalopathy","volume":"64","author":"Kinoshita","year":"2022","journal-title":"Pediatr. Int."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ashrafian, H., Docherty, L., Leo, V., Towlson, C., Neilan, M., Steeples, V., Lygate, C.A., Hough, T., Townsend, S., and Williams, D. (2010). A Mutation in the Mitochondrial Fission Gene Dnm1l Leads to Cardiomyopathy. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001000"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-3-030-27371-2_2","article-title":"The Genetic Landscape of Cardiomyopathies","volume":"Volume 7","author":"Erdmann","year":"2019","journal-title":"Genetic Causes of Cardiac Disease"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/978-3-030-27371-2_3","article-title":"Genetic Basis of Mitochondrial Cardiomyopathy","volume":"Volume 7","author":"Erdmann","year":"2019","journal-title":"Genetic Causes of Cardiac Disease"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1002\/ajmg.a.37624","article-title":"Postnatal Microcephaly and Pain Insensitivity Due to a de Novo Heterozygous DNM1L Mutation Causing Impaired Mitochondrial Fission and Function","volume":"170","author":"Sheffer","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1684\/epd.2022.1474","article-title":"DNM1L Mutation Presenting as Progressive Myoclonic Epilepsy Associated with Acute Febrile Infection-Related Epilepsy Syndrome","volume":"24","author":"Franklin","year":"2022","journal-title":"Epileptic Disord."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1111\/cge.14061","article-title":"Prevalence and Clinical Prediction of Mitochondrial Dis-orders in a Large Neuropediatric Cohort","volume":"100","author":"Johannsen","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_69","first-page":"887","article-title":"Analysis of DNM1L gene variant in a case of fatal encephalo-pathy caused by mitochondrial peroxidase division deficiency","volume":"38","author":"Chen","year":"2021","journal-title":"Chin. J. Med. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1684\/epd.2021.1375","article-title":"Epilepsia Partialis Continua Associated with the p.Arg403Cys Variant of the DNM1L Gene: An Unusual Clinical Progression with Two Episodes of Super-Refractory Status Epilepticus with a 13-Year Remission Interval","volume":"24","author":"Minghetti","year":"2022","journal-title":"Epileptic Disord."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1038\/ejhg.2015.243","article-title":"DNM1L-Related Mitochondrial Fission Defect Presenting as Refractory Epilepsy","volume":"24","author":"Vanstone","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Piccoli, C., Scrima, R., D\u2019Aprile, A., Chetta, M., Cela, O., Pacelli, C., Ripoli, M., D\u2019Andrea, G., Margaglione, M., and Bukvic, N. (2021). Pathogenic DNM1L Variant (1085G > A) Linked to Infantile Progressive Neurological Disorder: Evidence of Maternal Transmission by Germline Mosaicism and Influence of a Contemporary in Cis Variant (1535T > C). Genes, 12.","DOI":"10.3390\/genes12091295"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"32494","DOI":"10.1074\/jbc.M110.142430","article-title":"A Lethal de Novo Mutation in the Middle Domain of the Dynamin-Related GTPase Drp1 Impairs Higher Order Assembly and Mitochondrial Division","volume":"285","author":"Chang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/hmg\/ddz211","article-title":"Impaired Turnover of Hyperfused Mitochondria in Se-vere Axonal Neuropathy Due to a Novel DRP1 Mutation","volume":"29","author":"Longo","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0076-6879(02)50957-5","article-title":"Transformation of Yeast by Lithium Acetate\/Single-Stranded Carrier DNA\/Polyethylene Glycol Method","volume":"350","author":"Gietz","year":"2002","journal-title":"Methods Enzymol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ymeth.2010.02.023","article-title":"In Vivo Analysis of mtDNA Replication Defects in Yeast","volume":"51","author":"Baruffini","year":"2010","journal-title":"Methods"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/1097-0061(200011)16:15<1421::AID-YEA624>3.0.CO;2-U","article-title":"Mitochondria-Targeted Green Fluorescent Proteins: Convenient Tools for the Study of Organelle Biogenesis in Saccharomyces cerevisiae","volume":"16","author":"Westermann","year":"2000","journal-title":"Yeast"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/846\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:32:19Z","timestamp":1759919539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":77,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020846"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020846","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,20]]}}}