Nature Communications (Apr 2022)
Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy
- Hong Joo Kim,
- Payam Mohassel,
- Sandra Donkervoort,
- Lin Guo,
- Kevin O’Donovan,
- Maura Coughlin,
- Xaviere Lornage,
- Nicola Foulds,
- Simon R. Hammans,
- A. Reghan Foley,
- Charlotte M. Fare,
- Alice F. Ford,
- Masashi Ogasawara,
- Aki Sato,
- Aritoshi Iida,
- Pinki Munot,
- Gautam Ambegaonkar,
- Rahul Phadke,
- Dominic G. O’Donovan,
- Rebecca Buchert,
- Mona Grimmel,
- Ana Töpf,
- Irina T. Zaharieva,
- Lauren Brady,
- Ying Hu,
- Thomas E. Lloyd,
- Andrea Klein,
- Maja Steinlin,
- Alice Kuster,
- Sandra Mercier,
- Pascale Marcorelles,
- Yann Péréon,
- Emmanuelle Fleurence,
- Adnan Manzur,
- Sarah Ennis,
- Rosanna Upstill-Goddard,
- Luca Bello,
- Cinzia Bertolin,
- Elena Pegoraro,
- Leonardo Salviati,
- Courtney E. French,
- Andriy Shatillo,
- F. Lucy Raymond,
- Tobias B. Haack,
- Susana Quijano-Roy,
- Johann Böhm,
- Isabelle Nelson,
- Tanya Stojkovic,
- Teresinha Evangelista,
- Volker Straub,
- Norma B. Romero,
- Jocelyn Laporte,
- Francesco Muntoni,
- Ichizo Nishino,
- Mark A. Tarnopolsky,
- James Shorter,
- Carsten G. Bönnemann,
- J. Paul Taylor
Affiliations
- Hong Joo Kim
- Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital
- Payam Mohassel
- National Institute of Neurological Disorders and Stroke, National Institutes of Health
- Sandra Donkervoort
- National Institute of Neurological Disorders and Stroke, National Institutes of Health
- Lin Guo
- Department of Biochemistry & Biophysics, Perelman School of Medicine at the University of Pennsylvania
- Kevin O’Donovan
- Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital
- Maura Coughlin
- Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital
- Xaviere Lornage
- Département Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U1258, Centre National de la Recherche Scientifique UMR7104, Université de Strasbourg
- Nicola Foulds
- Wessex Clinical Genetics Services, Princess Anne Hospital, Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton
- Simon R. Hammans
- Wessex Neurological Centre, University Hospital Southampton
- A. Reghan Foley
- National Institute of Neurological Disorders and Stroke, National Institutes of Health
- Charlotte M. Fare
- Department of Biochemistry & Biophysics, Perelman School of Medicine at the University of Pennsylvania
- Alice F. Ford
- Department of Biochemistry & Biophysics, Perelman School of Medicine at the University of Pennsylvania
- Masashi Ogasawara
- Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP)
- Aki Sato
- Department of Neurology, Niigata City General Hospital
- Aritoshi Iida
- Medical Genome Center, NCNP, Kodaira
- Pinki Munot
- The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust
- Gautam Ambegaonkar
- Department of Paediatric Neurology, Cambridge University Hospital NHS Trust, Addenbrookes Hospital
- Rahul Phadke
- Division of Neuropathology, University College London Hospitals NHS Foundation Trust National Hospital for Neurology and Neurosurgery London, UK and Division of Neuropathology, UCL Institute of Neurology, Dubowitz Neuromuscular Centre
- Dominic G. O’Donovan
- Department of Histopathology Box 235, Level 5 John Bonnett Clinical Laboratories Addenbrooke’s Hospital
- Rebecca Buchert
- Institute of Medical Genetics and Applied Genomics, University of Tuebingen
- Mona Grimmel
- Institute of Medical Genetics and Applied Genomics, University of Tuebingen
- Ana Töpf
- John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust
- Irina T. Zaharieva
- The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust
- Lauren Brady
- Division of Neuromuscular & Neurometabolic Disorders, Department of Pediatrics, McMaster University, Hamilton Health Sciences Centre
- Ying Hu
- National Institute of Neurological Disorders and Stroke, National Institutes of Health
- Thomas E. Lloyd
- Department of Neurology, Johns Hopkins University School of Medicine
- Andrea Klein
- Division of Neuropaediatrics, Development and Rehabilitation, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern
- Maja Steinlin
- Division of Neuropaediatrics, Development and Rehabilitation, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern
- Alice Kuster
- Department of Neurometabolism, University Hospital of Nantes
- Sandra Mercier
- CHU Nantes, Service de génétique médicale, Centre de Référence des Maladies Neuromusculaires AOC
- Pascale Marcorelles
- Service d’anatomopathologie, CHU Brest and EA 4685 LIEN, Université de Bretagne Occidentale
- Yann Péréon
- CHU de Nantes, Centre de Référence des Maladies Neuromusculaires, Filnemus, Euro-NMD, Hôtel-Dieu
- Emmanuelle Fleurence
- Etablissement de Santé pour Enfants et Adolescents de la région Nantaise
- Adnan Manzur
- The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust
- Sarah Ennis
- Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton
- Rosanna Upstill-Goddard
- Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton
- Luca Bello
- Department of Neurosciences, DNS, University of Padova
- Cinzia Bertolin
- Clinical Genetics Unit, Department of Women and Children’s Health, University of Padova, IRP Città della Speranza
- Elena Pegoraro
- Department of Neurosciences, DNS, University of Padova
- Leonardo Salviati
- Clinical Genetics Unit, Department of Women and Children’s Health, CIR-Myo Myology Center, University of Padova, IRP Città della Speranza
- Courtney E. French
- Department of Paediatrics, University of Cambridge
- Andriy Shatillo
- Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine
- F. Lucy Raymond
- Cambridge Institute of Medical Research, University of Cambridge
- Tobias B. Haack
- Institute of Medical Genetics and Applied Genomics, University of Tuebingen
- Susana Quijano-Roy
- Neuromuscular Unit, Pediatric Neurology and ICU Department, Raymond Poincaré Hospital (UVSQ), AP-HP Université Paris-Saclay
- Johann Böhm
- Département Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U1258, Centre National de la Recherche Scientifique UMR7104, Université de Strasbourg
- Isabelle Nelson
- Sorbonne Université, INSERM, Centre of Research in Myology
- Tanya Stojkovic
- APHP, Centre de Référence des Maladies Neuromusculaires Nord/Est/Ile de France, Institut de Myologie, Sorbonne Université, Hôpital Pitié-Salpêtrière
- Teresinha Evangelista
- Unité de Morphologie Neuromusculaire, Institut de Myologie, Sorbonne Université, Hôpital Pitié-Salpêtrière
- Volker Straub
- John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust
- Norma B. Romero
- APHP, Centre de Référence des Maladies Neuromusculaires Nord/Est/Ile de France, Institut de Myologie, Sorbonne Université, Hôpital Pitié-Salpêtrière
- Jocelyn Laporte
- Département Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U1258, Centre National de la Recherche Scientifique UMR7104, Université de Strasbourg
- Francesco Muntoni
- The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust
- Ichizo Nishino
- Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP)
- Mark A. Tarnopolsky
- Division of Neuromuscular & Neurometabolic Disorders, Department of Pediatrics, McMaster University, Hamilton Health Sciences Centre
- James Shorter
- Department of Biochemistry & Biophysics, Perelman School of Medicine at the University of Pennsylvania
- Carsten G. Bönnemann
- National Institute of Neurological Disorders and Stroke, National Institutes of Health
- J. Paul Taylor
- Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital
- DOI
- https://doi.org/10.1038/s41467-022-30015-1
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 18
Abstract
Missense variants in RNA-binding proteins underlie many diseases. Here the authors report an oculopharyngeal muscular dystrophy caused by heterozygous frameshift mutations in HNRNPA2B1 that alter its nucleocytoplasmic transport dynamics and result in cytoplasmic accumulation of hnRNPA2 protein.
