ArticleCell2018
A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures.
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Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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92citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
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Who cites it
92 citing papers in PubMed, 145 citations in OpenAlex.
- The NORAD-Pumilio regulatory axis in the evolution of inclusion body myositis.Journal of neuropathology and experimental neurology · 2026Article
- Clinical Utility of Trio Exome Sequencing in Rwandan Children With Autism Spectrum Disorder.Molecular genetics & genomic medicine · 2026Article
- Functional divergence of Capicua isoforms explains differential tissue vulnerability in neurological disease.Genes & development · 2026Article
- How Early Should I Refer My Patient? The Benefits of a Quick Ophthalmic Referral in Spinocerebellar Ataxias, a Case Series and Literature Review.Brain sciences · 2026Article
- PUM1 and PUM2 promote translation of chromatin regulators to ensure mammalian spermatogenesis.Science advances · 2026Article
- Coordinated post-transcriptional regulation facilitates PD-L1 protein production and tumor immune suppression.Cancer letters · 2026Article
- Human pumilio proteins use fuzzy multivalent hydrophobic interactions to recruit the CCR4-NOT deadenylase complex to repress mRNAs.The Journal of biological chemistry · 2026Article
- Molecular interactome of HNRNPU reveals regulatory networks in neuronal differentiation and DNA methylation.Nucleic acids research · 2026Article
- Cytoplasmic poly-adenosine binding proteins modulate susceptibility of mRNAs to Pumilio-mediated decay.Nucleic acids research · 2026Article
- Crystal structures of Caenorhabditis elegans PUF-3 depict plasticity of RNA recognition that enables germline gene regulation.Nucleic acids research · 2026Article
- Chorea-predominant SCA5 mimicking Huntington's disease: A case report with a novelClinical parkinsonism & related disorders · 2026Article
- The Status and Future Directions of Treatments for Polyglutamine Spinocerebellar Ataxia: A Bibliometric and Visual Analysis.Current neuropharmacology · 2026Review
- Human Pumilio proteins use fuzzy multivalent hydrophobic interactions to recruit the CCR4-NOT deadenylase complex to repress mRNAs.bioRxiv : the preprint server for biology · 2025Article
- Functional divergence of Capicua isoforms explains differential tissue vulnerability in neurological disease.bioRxiv : the preprint server for biology · 2025Article
- Cytoplasmic poly-adenosine binding proteins modulate susceptibility of mRNAs to RNA-binding protein-directed decay.bioRxiv : the preprint server for biology · 2025Article
- Alpha-synuclein abundance and localization are regulated by the RNA-binding protein PUMILIO1.Cell reports · 2025Article
- Hepatocyte-derived Pumilio1-enriched exosomes inhibit HSC activation by suppressing tropomyosin-4 translation.Hepatology communications · 2025Article
- FGF14 GAA Intronic Expansion in Unsolved Adult-Onset Ataxia in the Care4Rare Canada Consortium.Annals of clinical and translational neurology · 2025Article
- The PUF RNA-binding protein, FBF-2, maintains stem cells without binding to RNA.RNA (New York, N.Y.) · 2025Article
- The regulatory role of lncRNA in tumor drug resistance: refracting light through a narrow aperture.Oncology research · 2025Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
41 authors at 11 institutions in 4 countries.
Vincenzo A GennarinoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA. Electronic address: vag2138@cumc.columbia.edu.
Elizabeth E PalmerSydney Children's Hospital, Randwick, NSW 2031, Australia; School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, NSW 2031, Australia; Genetics of Learning Disability Service, Waratah, NSW 2298, Australia.
Laura M McDonellChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Li WangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Carolyn J AdamskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Amanda KoireProgram in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA.
Lauren SeeDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Chun-An ChenDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Christian P SchaafDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jessica A PanzerDepartment of Pediatrics, Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ute MoogInstitute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
Shuang HaoJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Ann ByeSydney Children's Hospital, Randwick, NSW 2031, Australia; School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, NSW 2031, Australia.
Edwin P KirkSydney Children's Hospital, Randwick, NSW 2031, Australia; School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, NSW 2031, Australia; Genetics Laboratory, NSW Health Pathology East Randwick, Sydney, NSW, Australia.
Pawel StankiewiczDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics Laboratories, Baylor College of Medicine, Houston, TX 77030, USA.
Amy M BremanDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics Laboratories, Baylor College of Medicine, Houston, TX 77030, USA.
Arran McBrideChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Tejaswi KandulaSydney Children's Hospital, Randwick, NSW 2031, Australia; School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, NSW 2031, Australia.
Holly A DubbsDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Rebecca MacintoshSydney Children's Hospital, Randwick, NSW 2031, Australia.
Michael CardamoneSydney Children's Hospital, Randwick, NSW 2031, Australia; School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, NSW 2031, Australia.
Ying ZhuGenetics Laboratory, NSW Health Pathology East Randwick, Sydney, NSW, Australia.
Kevin YingKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Kerith-Rae DiasKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Megan T ChoGeneDx, 207 Perry Pkwy Gaithersburg, MD 20877, USA.
Lindsay B HendersonGeneDx, 207 Perry Pkwy Gaithersburg, MD 20877, USA.
Berivan BaskinGeneDx, 207 Perry Pkwy Gaithersburg, MD 20877, USA.
Paula MorrisKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Jiang TaoKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia.
Mark J CowleyKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia.
Marcel E DingerKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia.
Tony RoscioliSydney Children's Hospital, Randwick, NSW 2031, Australia; Genetics Laboratory, NSW Health Pathology East Randwick, Sydney, NSW, Australia; Neuroscience Research Australia and Prince of Wales Clinical School, University of New South Wales, Randwick, NSW 2031, Australia.
Oana CaluseriuDepartment of Medical Genetics, University of Alberta, AB T6G 2H7, Canada.
Oksana SuchowerskyDepartment of Medical Genetics, University of Alberta, AB T6G 2H7, Canada; Departments of Medicine (Neurology) and Pediatrics, University of Alberta, AB, Canada.
Rani K SachdevSydney Children's Hospital, Randwick, NSW 2031, Australia; School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, NSW 2031, Australia.
Olivier LichtargeDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jianrong TangJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Kym M BoycottChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
J Lloyd HolderJan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Huda Y ZoghbiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: hzoghbi@bcm.edu.
Baylor College of Medicine · USGarvan Institute of Medical Research · AUUNSW Sydney · AUNew South Wales Department of Health · AUUniversity of Ottawa · CAChildren's Hospital of Philadelphia · USUniversity of Alberta · CAHeidelberg University · DEHoward Hughes Medical Institute · USSydney Children's Hospital · AUTexas Medical Center · US
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9MTraining Program in Neurodevelopmental DisabilitiesT32NS007413 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI AMELIA J EISCH, ERIC D MARSH · 1998 to 2026
$8.9MSteps towards a paternal gene activation therapy for Angelman syndromeU54HD083092 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI NELSON, DAVID LOREN, SAMACO, RODNEY C · 2014 to 2019
$7.8MFunctional Determinnats in G Protein-coupled ReceptorsR01GM066099 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI LICHTARGE, OLIVIER · 2003 to 2022
$7.5MComparative genomics of protein structure and functionR01GM079656 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI LICHTARGE, OLIVIER · 2007 to 2019
$4.3MMOLECULAR STUDIES OF SPINOCEREBELLAR ATAXIS TYPE IR37NS027699 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI ZOGHBI, HUDA Y · 2015 to 2021
$2.8MRESCUING MOTOR DEFICITS IN SHANK3 RELEATED DISORDERSK08NS091381 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI HOLDER, JIMMY L · 2015 to 2019
$908kCIHRHoward Hughes Medical InstituteNCI NIH HHS P30 CA125123NICHD NIH HHS U54 HD083092NIGMS NIH HHS R01 GM066099NIGMS NIH HHS R01 GM079656NINDS NIH HHS K08 NS091381NINDS NIH HHS R37 NS027699NINDS NIH HHS T32 NS007413
Abstract
Certain mutations can cause proteins to accumulate in neurons, leading to neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency of its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration in mice. We therefore searched for human patients with PUM1 mutations. We identified eleven individuals with either PUM1 deletions or de novo missense variants who suffer a developmental syndrome (Pumilio1-associated developmental disability, ataxia, and seizure; PADDAS). We also identified a milder missense mutation in a family with adult-onset ataxia with incomplete penetrance (Pumilio1-related cerebellar ataxia, PRCA). Studies in patient-derived cells revealed that the missense mutations reduced PUM1 protein levels by ∼25% in the adult-onset cases and by ∼50% in the infantile-onset cases; levels of known PUM1 targets increased accordingly. Changes in protein levels thus track with phenotypic severity, and identifying posttranscriptional modulators of protein expression should identify new candidate disease genes.
Indexed as
Genetic Predisposition to DiseaseAdolescentAdultAged, 80 and overAge of OnsetAnimalsBase SequenceChildChild, PreschoolDevelopmental DisabilitiesEvolution, MolecularFemaleGene DeletionHaploinsufficiencyHEK293 CellsHumansPUM1 protein, humanpumilio 1 protein, mouseRNA-Binding ProteinsataxiaAtaxin-1chromosome 1p35.2copy number variantsdevelopmental delayintellectual disabilityPADDASPRCAPumilio1RNA-binding proteinsseizures
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