ArticleAmerican journal of human genetics2025
Bi-allelic variants in MRPL49 cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.
Abstract read
In one paragraph
Article in American journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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
5 citing papers in PubMed.
- Environmental PFOA Exposure Alters Early Developmental Programming during the Maternal-Zygotic Transition.bioRxiv : the preprint server for biology · 2026Article
- A biallelic MRPL42 variant causes a combined oxidative phosphorylation deficiency syndrome revealed by multi-omics.NPJ genomic medicine · 2026Article
- The maternal-to-zygotic transition is a critical window for PFOA-induced disruption of developmental programming.Frontiers in cell and developmental biology · 2026Article
- Neurogenetic Disorders with Hearing Loss: Mechanisms, Classifications, and Emerging Insights.Current neurology and neuroscience reports · 2025Review
- Endocrinopathy, dystonia, and tremor in a patient with homozygous MRPL49 mutation.Acta neurologica Belgica · 2025Article
Corrections and comments
- Update of
Authors and funding
46 authors.
Huw B ThomasDivision of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
Leigh A M DemainDivision of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
Alfredo Cabrera-OreficeCentre for Functional Proteomics, Institute for Cardiovascular Physiology, Medical Faculty, Goethe University, 60596 Frankfurt am Main, Germany; Institute of Biochemistry, Medical Faculty, Justus-Liebig-University, 35392 Giessen, Germany.
Isabelle SchrauwenDepartment of Translational Neurosciences, University of Arizona College of Medicine Phoenix, Phoenix, AZ, USA.
Hanan E ShamseldinDepartment of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Alessandro ReaDivision of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
Thashi BharadwajCenter for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA.
Thomas B SmithDivision of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
Monika OláhováDepartment of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, UK; Mitochondrial Research Group, Clinical and Translational Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Kyle ThompsonMitochondrial Research Group, Clinical and Translational Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Langping HeNHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
Namanpreet KaurDepartment of Medical Genetics, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Anju ShuklaDepartment of Medical Genetics, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Musaad AbukhalidDepartment of Neuroscience, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Muhammad AnsarDepartment of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad 45320, Pakistan.
Sakina RehmanDepartment of Otorhinolaryngology - Head & Neck Surgery, School of Medicine University of Maryland, Baltimore, MD, USA; Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
Saima RiazuddinDepartment of Otorhinolaryngology - Head & Neck Surgery, School of Medicine University of Maryland, Baltimore, MD, USA; Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
Firdous AbdulwahabDepartment of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Janine M SmithSpecialty of Genomic Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2000, Australia; Western Sydney Genetics Program, Department of Clinical Genetics, Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Zornitza StarkVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Flemington Road, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia.
Hanifenur MancilarAcıbadem Labgen Genetic Diagnosis Center, Istanbul, Türkiye.
Sait TumerAcıbadem Labgen Genetic Diagnosis Center, Istanbul, Türkiye.
Fatma N EsenAcıbadem Labgen Genetic Diagnosis Center, Istanbul, Türkiye.
Eyyup UctepeAcıbadem Labgen Genetic Diagnosis Center, Istanbul, Türkiye.
Vehap TopcuAcıbadem Labgen Genetic Diagnosis Center, Istanbul, Türkiye.
Ahmet YesilyurtAcıbadem Labgen Genetic Diagnosis Center, Istanbul, Türkiye.
Erum AfzalDepartment of Development Pediatrics, The Children's Hospital and The Institute of Child Health, Multan, Pakistan.
Mehri SalariDepartment of Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Christopher CarrollGenetics Section, Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK.
Giovanni ZifarelliCENTOGENE GmbH, Am Strande 7, 18055 Rostock, Germany.
Peter BauerCENTOGENE GmbH, Am Strande 7, 18055 Rostock, Germany.
Deniz KorCukurova University, Medical Faculty, Department of Pediatric Metabolism and Nutrition, Adana, Turkey.
Fatma D BulutCukurova University, Medical Faculty, Department of Pediatric Metabolism and Nutrition, Adana, Turkey.
Henry HouldenDepartment of Neuromuscular Diseases, University College London, Queen Square, Institute of Neurology, London WC1N 3BG, UK.
Reza MaroofianDepartment of Neuromuscular Diseases, University College London, Queen Square, Institute of Neurology, London WC1N 3BG, UK.
Samantha CarreraGenome Editing Unit Core Facility, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Wyatt W YueNewcastle University Biosciences Institute, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Kevin J MunroManchester Centre for Audiology and Deafness (ManCAD), School of Health Sciences, University of Manchester, Manchester, UK.
Fowzan S AlkurayaDepartment of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Peter JamiesonDepartment of Radiology, Manchester University Hospital NHS Foundation Trust, Manchester M13 9PW, UK.
Zubair M AhmedDepartment of Otorhinolaryngology - Head & Neck Surgery, School of Medicine University of Maryland, Baltimore, MD, USA; Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
Suzanne M LealCenter for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA; Taub Institute for Alzheimer's Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Robert W TaylorMitochondrial Research Group, Clinical and Translational Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
Ilka WittigCentre for Functional Proteomics, Institute for Cardiovascular Physiology, Medical Faculty, Goethe University, 60596 Frankfurt am Main, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main, 60596 Frankfurt am Main, Germany.
Raymond T O'KeefeDivision of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK. Electronic address: rokeefe@manchester.ac.uk.
William G NewmanDivision of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK. Electronic address: william.newman@manchester.ac.uk.
Funding
Genetics and Functional Studies of Autosomal Recessive Neurological DisordersR01NS107428 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI Saima Riazuddin · 2018 to 2026
$4.7MElucidating the Genetic Etiology of Intellectual Disability in African, Asian, and European FamiliesR01HD109342 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SUZANNE M LEAL, Isabelle Veerle Suzanne Schrauwen · 2023 to 2026
$2.5MNICHD NIH HHS R01 HD109342NINDS NIH HHS R01 NS107428
Abstract
Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder that is clinically and genetically heterogeneous. Genome sequencing identified bi-allelic MRPL49 variants in individuals from nine unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly, and retinal dystrophy. Complexome profiling of fibroblasts from affected individuals revealed reduced levels of the small mitochondrial ribosomal subunits and a more pronounced reduction of the large mitochondrial ribosomal subunits. There was no evidence of altered mitoribosomal assembly. The reductions in levels of oxidative phosphorylation (OXPHOS) enzyme complexes I and IV are consistent with a form of COXPD associated with bi-allelic MRPL49 variants, expanding the understanding of how disruption of the mitochondrial ribosomal large subunit results in multisystem phenotypes.
Indexed as
Gonadal Dysgenesis, 46,XXHearing Loss, SensorineuralMitochondrial ProteinsPrimary Ovarian InsufficiencyRibosomal ProteinsAdolescentAdultAllelesChildChild, PreschoolFemaleHumansInfantMaleMutationOxidative PhosphorylationMitochondrial ProteinsRibosomal Proteinscombined oxidative phosphorylation deficiencylearning disabilityleukodystrophymitochondriamitoribosomeMRPL49Perrault syndromeprimary ovarian insufficiencyrare diseasesensorineural hearing loss
Identifiers
What Socratic 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 Socratic graph.