Autosomal recessive VWA1 -related disorder: comprehensive analysis of phenotypic variability and genetic mutations.

Autor:	Nagy S; Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.; Department of Neurology, University Hospital Basel, University of Basel, Basel 4031, Switzerland., Pagnamenta AT; NIHR Oxford Biomedical Research Centre, Centre for Human Genetics, University of Oxford, Oxford OX3 9DU, UK., Cali E; Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK., Braakman HMH; Department of Pediatric Neurology, Amalia Children's Hospital, Radboud University Medical Center & Donders Institute for Brain, Cognition and Behavior, Nijmegen 6525 GA, The Netherlands., Wijntjes J; Department of Neurology and Clinical Neurophysiology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen 6525 GD, The Netherlands., Kusters B; Department of Pathology, Radboudumc, Nijmegen 6525 GA, The Netherlands., Gotkine M; Department of Neurology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel., Elpeleg O; Department of Genetics, Hadassah Medical Center, Hebrew University Medical Center, Jerusalem 9574869, Israel., Meiner V; Department of Genetics, Hadassah Medical Center, Hebrew University Medical Center, Jerusalem 9574869, Israel., Lenberg J; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA., Wigby K; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.; Rady Children's Hospital, San Diego, CA 92123, USA.; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA., Friedman J; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA., Perry LD; The Dubowitz Neuromuscular Centre, UCL Great Ormond Street, Great Ormond Street Hospital, London WC1N 1EH, UK.; NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.; MRC International Centre for Genomic Medicine in Neuromuscular Diseases, London WC1N 3BG, UK., Rossor AM; Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK., Uhrova Meszarosova A; Neurogenetic Laboratory, Department of Paediatric Neurology, and Institute of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague 150 06, Czech Republic., Thomasova D; Neurogenetic Laboratory, Department of Paediatric Neurology, and Institute of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague 150 06, Czech Republic., Jacob S; Department of Neurology, University Hospitals Birmingham, Birmingham B15 2TT, UK.; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., O'Driscoll M; West Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham B15 2TG, UK., De Simone L; Division of Genetics, Genomics, and Metabolism, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.; Division of Neurology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA., Grange DK; Department of Neurology at Washington University, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63108, USA., Sommerville R; Department of Neurology at Washington University, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63108, USA., Firoozfar Z; Palindrome, Isfahan 83714, Iran., Alavi S; Palindrome, Isfahan 83714, Iran., Mazaheri M; Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 97514, Iran.; Dr. Mazaheri's Medical Genetics Lab, Yazd 97514, Iran., Parmar JM; Rare Disease Genetics and Functional Genomics Group, Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia.; Centre for Medical Research, University of Western Australia, Nedlands, WA 6009, Australia., Lamont PJ; Royal Perth Hospital, Perth, WA 6000, Australia., Pini V; The Dubowitz Neuromuscular Centre, UCL Great Ormond Street, Great Ormond Street Hospital, London WC1N 1EH, UK., Sarkozy A; The Dubowitz Neuromuscular Centre, UCL Great Ormond Street, Great Ormond Street Hospital, London WC1N 1EH, UK.; MRC International Centre for Genomic Medicine in Neuromuscular Diseases, London WC1N 3BG, UK., Muntoni F; The Dubowitz Neuromuscular Centre, UCL Great Ormond Street, Great Ormond Street Hospital, London WC1N 1EH, UK.; NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK., Ravenscroft G; Rare Disease Genetics and Functional Genomics Group, Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia.; Centre for Medical Research, University of Western Australia, Nedlands, WA 6009, Australia., Jones E; Genomics Medicine Ireland, Dublin D18 K7W4, Ireland., O'Rourke D; Children's Health Ireland at Temple Street, Dublin, Dublin D01 XD99, Ireland., Nel M; Neurogenomics Lab, Neuroscience Institute, University of Cape Town, Cape Town 7935, South Africa.; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7935, South Africa., Heckmann JM; Neurology Research Group, Neuroscience Institute, University of Cape Town, Cape Town 7935, South Africa., Kvalsund M; Department of Neurology, University of Rochester Medical Center, Rochester, NY 14618, USA.; Department of Internal Medicine, University of Zambia School of Medicine, Ridgeway, Lusaka, Zambia., Kapapa MM; Department of Physiotherapy, University of Zambia School of Health Sciences, Lusaka, Zambia., Wa Somwe S; Department of Paediatrics and Child Health, School of Medicine and Health Sciences, University of Lusaka, Lusaka, Zambia., Bearden DR; Department of Neurology, University of Rochester Medical Center, Rochester, NY 14618, USA.; Department of Educational Psychology, University of Zambia, Lusaka, Zambia., Çakar A; Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.; Neuromuscular Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey., Childs AM; Department of Paediatric Neurology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3EX, UK., Horvath R; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 2PY, UK., Reilly MM; Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK., Houlden H; Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK., Maroofian R; Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2024 Oct 28; Vol. 6 (6), pp. fcae377. Date of Electronic Publication: 2024 Oct 28 (Print Publication: 2024).
DOI:	10.1093/braincomms/fcae377
Abstrakt:	A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain-containing 1 ( VWA1 ). This study further delineates the disease characteristics in a cohort of 20 individuals diagnosed through genome or exome sequencing, incorporating neurophysiological, laboratory and imaging data, along with data from previously reported cases across three different studies. Newly reported clinical features include hypermobility/hyperlaxity, axial weakness, dysmorphic signs, asymmetric presentation, dystonic features and, notably, upper motor neuron signs. Foot drop, foot deformities and distal leg weakness followed by early proximal leg weakness are confirmed to be initial manifestations. Additionally, this study identified 11 novel VWA1 variants, reaffirming the 10 bp insertion-induced p.Gly25ArgfsTer74 as the most prevalent disease-causing allele, with a carrier frequency of ∼1 in 441 in the UK and Western European population. Importantly, VWA1-related pathology may mimic various neuromuscular conditions, advocating for its inclusion in diverse gene panels spanning hereditary neuropathies to muscular dystrophies. The study highlights the potential of lower quality control filters in exome analysis to enhance diagnostic yield of VWA1 disease that may account for up to 1% of unexplained hereditary neuropathies. Competing Interests: The authors report no competing interests. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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