ArticleNature communications2015
Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
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.
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.
Who cites it
106 citing papers in PubMed, 177 citations in OpenAlex.
- Alpha-like subunits of multisubunit RNA polymerases: insights into structure, function, and disease.RNA biology · 2026Review
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Monoallelic POLR3A Variants Cause Early-Onset Peripheral Neuropathy.Annals of neurology · 2026Article
- Current gene panels for female infertility: gaps between evidence and clinical application.Journal of assisted reproduction and genetics · 2026Review
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- RNA-based discovery and correction of splicing defects caused byMolecular therapy. Nucleic acids · 2026Article
- Study of POLR3A variants in a family trio suggests mutation-specific pathogenetic mechanisms: insights from integrative OMIC approaches.Cell communication and signaling : CCS · 2026Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Overview of genetic variants in a cohort of Iranian patients with leukodystrophy.Scientific reports · 2025Article
- Genome-wide DNA methylation analysis of CBCVd-infected hop plants (Microbiology spectrum · 2025Article
- POLR3-Related Leukodystrophy: A Qualitative Study on Parents' Experiences With the Health Care System.Pediatric neurology · 2025Article
- Bi-allelic variants in BRF2 are associated with perinatal death and craniofacial anomalies.Genome medicine · 2025Article
- Biallelic variants inBrain communications · 2025Article
- Stress and Quality of Life of Parents of Children With POLR3-Related Leukodystrophy: A Cross-Sectional Pilot Study.Journal of child neurology · 2025Article
- Towards a Treatment for Leukodystrophy Using Cell-Based Interception and Precision Medicine.Biomolecules · 2024Review
- Polymerase I as a Target for Treating Neurodegenerative Disorders.Biomedicines · 2024Review
- Biallelic variants identified in 36 Pakistani families and trios with autism spectrum disorder.Scientific reports · 2024Article
- The 37TrillionCells initiative for improving global healthcare via cell-based interception and precision medicine: focus on neurodegenerative diseases.Molecular brain · 2024Review
- Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation.Scientific reports · 2024Article
- ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans.Genome biology · 2024Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 17 institutions in 9 countries.
Isabelle Thiffault1] Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada. [2] Service de Génétique, Centre Hospitalier Universitaire Sainte-Justine, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec H3T1C5, Canada. [3] Center for Pediatric Genomic Medicine, Children's Mercy Hospital, 2420 Pershing Road, Suite 421, Kansas City, Missouri 64108, USA.
Nicole I WolfDepartment of Child Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands.ORCID 0000000317210728
Diane ForgetTranslational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins ouest, Montréal, Québec H2W 1R7, Canada.
Kether GuerreroDepartment of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada.
Luan T TranDepartment of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada.
Karine ChoquetNeurogenetics of Motion Laboratory, Montreal Neurological Institute, 3801 University Street, McGill University, Montreal, Quebec H3A 2B4, Canada.
Mathieu Lavallée-AdamDepartment of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road SR302, La Jolla, California 92037, USA.
Christian PoitrasTranslational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins ouest, Montréal, Québec H2W 1R7, Canada.
Bernard BraisNeurogenetics of Motion Laboratory, Montreal Neurological Institute, 3801 University Street, McGill University, Montreal, Quebec H3A 2B4, Canada.
Grace YoonDivision of Neurology and Clinical and Metabolic Genetics, the Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Laszlo SztrihaDepartment of Paediatrics, Faculty of Medicine, University of Szeged, Temesvári krt. 35-37, Szeged H-6726, Hungary.
Richard I Webster1] T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia. [2] Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead New South Wales 2145, Australia.
Dagmar TimmannDepartment of Neurology, University Clinic Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany.
Bart P van de WarrenburgDepartment of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, PO Box 9101, Nijmegen 6500 HB, The Netherlands.
Jürgen SeegerDepartment of Pediatrics and Adolescent Medicine, Deutsche KlinikfürDiagnostik, Wiesbaden 65191, Germany.
Alíz ZimmermannDepartment of Paediatrics, Faculty of Medicine, University of Szeged, Temesvári krt. 35-37, Szeged H-6726, Hungary.
Adrienn MátéDepartment of Neurosurgery, Faculty of Medicine, University of Szeged, 6 Semmelweis Street, Szeged H-6725, Hungary.
Cyril GoizetService de Génétique, Hôpital Pellegrin, CHU Bordeaux and University Bordeaux, Laboratoire MRGM (EA4576), Bordeaux 33076, France.
Eva FungDepartment of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR China.
Marjo S van der KnaapDepartment of Child Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands.
Sébastien Fribourg1] Université de Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac F-33607, France. [2] Institut National de la Santé Et de la Recherche Médicale, INSERM-U869, ARNA Laboratory, Bordeaux F-33000, France.
Adeline Vanderver1] Center for Genetic Medicine Research, Children's National, 111 Michigan Avenue Northwest, Washington, District of Columbia 20010, USA. [2] Department of Neurology, Children's National, 111 Michigan Avenue Northwest, Washington, District of Columbia 20010, USA. [3] George Washington University, School of Medicine, Washington, District of Columbia 20052, USA.
Cas SimonsInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
Ryan J Taft1] George Washington University, School of Medicine, Washington, District of Columbia 20052, USA. [2] Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia. [3] Departments of Integrative Systems Biology and Pediatrics, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia 20037, USA. [4] Illumina Inc., 5200 Illumina Way, San Diego, California 92122, USA.
John R YatesDepartment of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road SR302, La Jolla, California 92037, USA.
Benoit Coulombe1] Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins ouest, Montréal, Québec H2W 1R7, Canada. [2] Department of Biochemistry, Université de Montréal, Pavillon Roger-Gaudry, CP 6128, Succ Centre-Ville, Montreal, Québec H3C 3J7, Canada.
Geneviève BernardDepartment of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada.
Montreal Children's Hospital · CAMontreal Clinical Research Institute · CAUniversity of Szeged · HUAmsterdam Neuroscience · NLMontreal Neurological Institute and Hospital · CAScripps Research Institute · USThe University of Queensland · AUChildren's Hospital at Westmead · AUChildren's Mercy Hospital · USChildren's National · USChinese University of Hong Kong · HKDeutsche Klinik für Diagnostik · DEHôpital Pellegrin · FRRadboud University Nijmegen · NLUniversité de Bordeaux · FRUniversity of Duisburg-Essen · DEUniversity of Toronto · CA
Funding
TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7MClinical and Translational Science Institute at Children's NationalUL1TR000075 · NCATS · CHILDREN'S RESEARCH INSTITUTE · PI GUAY-WOODFORD, LISA MARIE · 2012 to 2015
$13.7MProteogenetics of Autism Spectrum DisordersR01MH100175 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI MUOTRI, ALYSSON R., YATES III, JOHN R · 2013 to 2025
$7.4MQuantitative Proteome Analysis of Brain DevelopmentR01MH067880 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI YATES III, JOHN R · 2003 to 2017
$7.1MCanadian Institutes of Health Research MOP-G-287547NCATS NIH HHS UL1 TR000075NCATS NIH HHS UL1TR000075NHLBI NIH HHS HHSN268201000035CNIGMS NIH HHS P41 GM103533NIMH NIH HHS R01 MH067880NIMH NIH HHS R01 MH100175PHS HHS HHSN268201000035C
Abstract
A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.
Indexed as
Genes, RecessiveGenetic Predisposition to DiseaseDNA-Directed RNA PolymerasesGene Expression Regulation, EnzymologicHereditary Central Nervous System Demyelinating DiseasesHomozygoteHumansMutationRNA Polymerase IIIDNA-Directed RNA PolymerasesPOLR1C protein, humanRNA Polymerase III
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
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.