CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders.

Autor:	van Karnebeek CDM; Amsterdam UMC location University of Amsterdam, Departments of Pediatrics and Human Genetics, Emma Center for Personalized Medicine, Amsterdam, The Netherlands; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, The Netherlands; Departments of Medical Genetics and Pediatrics, Centre for Molecular Medicine and Therapeutics, Faculty of Pharmaceutical Science, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada; United for Metabolic Diseases, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands., Tarailo-Graovac M; Departments of Medical Genetics and Biochemistry & Molecular Biology, Alberta Children's Hospital Research Institute (ACHRI), Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Leen R; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands., Meinsma R; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands., Correard S; Departments of Medical Genetics and Pediatrics, Centre for Molecular Medicine and Therapeutics, Faculty of Pharmaceutical Science, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada., Jansen-Meijer J; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands., Prykhozhij SV; Faculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada., Pena IA; The Picower Institute for Learning and Memory, Massachusetts Institute of Technology-MIT, Boston, MA., Ban K; Faculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada., Schock S; Faculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada., Saxena V; Department of Biology, University of Ottawa, Ottawa, ON, Canada., Pras-Raves ML; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands., Drögemöller BI; Rady Faculty of Health Sciences, Department of Biochemistry and Medical Genetics, Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada., Grootemaat AE; Amsterdam UMC Location University of Amsterdam, Department of Medical Biology, Amsterdam, The Netherlands., van der Wel NN; Amsterdam UMC Location University of Amsterdam, Department of Medical Biology, Amsterdam, The Netherlands., Dobritzsch D; Uppsala University, Department of Chemistry, Biomedical Center, Uppsala, Sweden., Roseboom W; Swammerdam Institute for Life Sciences, University of Amsterdam, Laboratory for Mass Spectrometry of Biomolecules, Amsterdam, The Netherlands., Schomakers BV; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands., Jaspers YRJ; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands., Zoetekouw L; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands., Roelofsen J; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands., Ferreira CR; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD., van der Lee R; Departments of Medical Genetics and Pediatrics, Centre for Molecular Medicine and Therapeutics, Faculty of Pharmaceutical Science, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada., Ross CJ; Departments of Medical Genetics and Pediatrics, Centre for Molecular Medicine and Therapeutics, Faculty of Pharmaceutical Science, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada., Kochan J; Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biochemistry, Kraków, Poland., McIntyre RL; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands., van Klinken JB; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., van Weeghel M; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands., Kramer G; Swammerdam Institute for Life Sciences, University of Amsterdam, Laboratory for Mass Spectrometry of Biomolecules, Amsterdam, The Netherlands., Weschke B; Department of Neuropediatrics, Charité University Medicine Berlin, Berlin, Germany., Labrune P; APHP-Université Paris-Saclay, Hôpital Antoine Béclère, Centre de Référence Maladies Héréditaires du Métabolisme Hépatique, Service de Pédiatrie, Clamart, and Paris-Saclay University, and INSERM U 1195, Clamart, France., Willemsen MA; Department of Pediatric Neurology and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands., Riva D; Neurogenetic Syndromes and Autism Spectrum Disorders Unit, Fondazione IRCCS Istituto Neurologico 'Carlo Besta,' Milan, Italy., Garavaglia B; Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico 'Carlo Besta,' Milan, Italy., Moeschler JB; Geisel School of Medicine, Dartmouth College and Departments of Pediatrics, Children's Hospital at Dartmouth, Lebanon, NH., Filiano JJ; Geisel School of Medicine, Dartmouth College and Departments of Pediatrics, Children's Hospital at Dartmouth, Lebanon, NH., Ekker M; Department of Biology, University of Ottawa, Ottawa, ON, Canada., Berman JN; Faculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada., Dyment D; Faculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada., Vaz FM; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands., Wasserman WW; Departments of Medical Genetics and Pediatrics, Centre for Molecular Medicine and Therapeutics, Faculty of Pharmaceutical Science, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada., Houtkooper RH; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands., van Kuilenburg ABP; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands. Electronic address: a.b.vankuilenburg@amsterdamumc.nl.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Jun; Vol. 26 (6), pp. 101104. Date of Electronic Publication: 2024 Feb 24.
DOI:	10.1016/j.gim.2024.101104
Abstrakt:	Purpose: The functionality of many cellular proteins depends on cofactors; yet, they have only been implicated in a minority of Mendelian diseases. Here, we describe the first 2 inherited disorders of the cytosolic iron-sulfur protein assembly system. Methods: Genetic testing via genome sequencing was applied to identify the underlying disease cause in 3 patients with microcephaly, congenital brain malformations, progressive developmental and neurologic impairments, recurrent infections, and a fatal outcome. Studies in patient-derived skin fibroblasts and zebrafish models were performed to investigate the biochemical and cellular consequences. Results: Metabolic analysis showed elevated uracil and thymine levels in body fluids but no pathogenic variants in DPYD, encoding dihydropyrimidine dehydrogenase. Genome sequencing identified compound heterozygosity in 2 patients for missense variants in CIAO1, encoding cytosolic iron-sulfur assembly component 1, and homozygosity for an in-frame 3-nucleotide deletion in MMS19, encoding the MMS19 homolog, cytosolic iron-sulfur assembly component, in the third patient. Profound alterations in the proteome, metabolome, and lipidome were observed in patient-derived fibroblasts. We confirmed the detrimental effect of deficiencies in CIAO1 and MMS19 in zebrafish models. Conclusion: A general failure of cytosolic and nuclear iron-sulfur protein maturation caused pleiotropic effects. The critical function of the cytosolic iron-sulfur protein assembly machinery for antiviral host defense may well explain the recurrent severe infections occurring in our patients. Competing Interests: Conflict of Interest The authors declare no conflicts of interest. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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