Evidence map›Paper›PMID 38411040›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2024

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

Clara D M van Karnebeek, Maja Tarailo-Graovac, René Leen, Rutger Meinsma, Solenne Correard, Judith Jansen-Meijer, Sergey V Prykhozhij, Izabella A Pena, Kevin Ban, Sarah Schock and 33 more

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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors at 19 institutions in 8 countries.

Clara D M van KarnebeekAmsterdam 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.
Maja Tarailo-GraovacDepartments of Medical Genetics and Biochemistry & Molecular Biology, Alberta Children's Hospital Research Institute (ACHRI), Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
René LeenAmsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands.
Rutger MeinsmaAmsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
Solenne CorreardDepartments 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.
Judith Jansen-MeijerAmsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
Sergey V PrykhozhijFaculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada.
Izabella A PenaThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology-MIT, Boston, MA.
Kevin BanFaculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada.
Sarah SchockFaculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada.
Vishal SaxenaDepartment of Biology, University of Ottawa, Ottawa, ON, Canada.
Mia L Pras-RavesAmsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands.
Britt I DrögemöllerRady Faculty of Health Sciences, Department of Biochemistry and Medical Genetics, Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.
Anita E GrootemaatAmsterdam UMC Location University of Amsterdam, Department of Medical Biology, Amsterdam, The Netherlands.
Nicole N van der WelAmsterdam UMC Location University of Amsterdam, Department of Medical Biology, Amsterdam, The Netherlands.
Doreen DobritzschUppsala University, Department of Chemistry, Biomedical Center, Uppsala, Sweden.
Winfried RoseboomSwammerdam Institute for Life Sciences, University of Amsterdam, Laboratory for Mass Spectrometry of Biomolecules, Amsterdam, The Netherlands.
Bauke V SchomakersAmsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands.
Yorrick R J JaspersAmsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands; Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
Lida ZoetekouwAmsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
Jeroen RoelofsenAmsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
Carlos R FerreiraNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Robin van der LeeDepartments 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.
Colin J RossDepartments 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.
Jakub KochanJagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biochemistry, Kraków, Poland.
Rebecca L McIntyreAmsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
Jan B van KlinkenAmsterdam 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.
Michel van WeeghelAmsterdam 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.
Gertjan KramerSwammerdam Institute for Life Sciences, University of Amsterdam, Laboratory for Mass Spectrometry of Biomolecules, Amsterdam, The Netherlands.
Bernhard WeschkeDepartment of Neuropediatrics, Charité University Medicine Berlin, Berlin, Germany.
Philippe LabruneAPHP-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.
Michèl A WillemsenDepartment of Pediatric Neurology and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Daria RivaNeurogenetic Syndromes and Autism Spectrum Disorders Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milan, Italy.
Barbara GaravagliaMedical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milan, Italy.
John B MoeschlerGeisel School of Medicine, Dartmouth College and Departments of Pediatrics, Children's Hospital at Dartmouth, Lebanon, NH.
James J FilianoGeisel School of Medicine, Dartmouth College and Departments of Pediatrics, Children's Hospital at Dartmouth, Lebanon, NH.
Marc EkkerDepartment of Biology, University of Ottawa, Ottawa, ON, Canada.
Jason N BermanFaculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada.
David DymentFaculty of Medicine, CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada.
Frédéric M VazAmsterdam 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.
Wyeth W WassermanDepartments 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.
Riekelt H HoutkooperEmma 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.
André B P van KuilenburgAmsterdam 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.
Amsterdam University Medical Centers · NLUniversity of Ottawa · CANetherlands Metabolomics Centre · NLUniversity of British Columbia · CAAmsterdam Neuroscience · NLDartmouth College · USFondazione IRCCS Istituto Neurologico Carlo Besta · ITUniversity of Amsterdam · NLCharité - Universitätsmedizin Berlin · DEChildren's Hospital Research Institute of Manitoba · CAEmma Kinderziekenhuis · NLInserm · FRJagiellonian University · PLLeiden University Medical Center · NLMassachusetts Institute of Technology · USNational Institutes of Health · USRadboud University Nijmegen · NLUniversity of Calgary · CAUppsala University · SE

Funding

Skeletal and Metabolic Translational MedicineZIAHD009024 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI FERREIRA, CARLOS · 2025 to 2025
$2.5M
Intramural NIH HHS ZIA HD009024
6 · The paper itself

Abstract

purposeThe 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.

methodsGenetic 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.

resultsMetabolic 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.

conclusionA 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.

Indexed as

Iron-Sulfur ProteinsTranscription FactorsZebrafishAnimalsCytosolFemaleFibroblastsHumansInfantMaleMetallochaperonesMicrocephalyNeurodegenerative DiseasesPhenotypeCIAO1 protein, humanIron-Sulfur ProteinsMetallochaperonesMMS19 protein, humanTranscription FactorsCIAO1 and MMS19CofactorInfectionIron-sulfur clustersNeurodegeneration

Identifiers

PMID38411040
PMCPMC11788579
OpenAlexW4392139085

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.