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Beta-propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation
Open accessAbstract
Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.
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“Brain imaging shows iron accumulation in the substantia nigra and globus pallidus of patients with β-propeller protein-associated neurodegeneration.183”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [183]
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A method and server for predicting damaging missense mutations.
Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., & Sunyaev, S. R. (2010) · Nature Methods · doi:10.1038/nmeth0410-248 · Cited by 13,194
SIFT: predicting amino acid changes that affect protein function
Ng, P. C. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg509 · Cited by 6,601
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,551
Network organization of the human autophagy system
Behrends, C., Sowa, M. E., Gygi, S. P., & Harper, J. W. (2010) · Nature · doi:10.1038/nature09204 · Cited by 1,554
Capriotti, E., Calabrese, R., & Casadio, R. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl423 · Cited by 940
PMUT: a web-based tool for the annotation of pathological mutations on proteins
Ferrer‐Costa, C., Gelpí, J. L., Zamakola, L., Parraga, I., de la Cruz, X., & Orozco, M. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti486 · Cited by 495
Clinical and genetic delineation of neurodegeneration with brain iron accumulation
Gregory, A., Polster, B. J., & Hayflick, S. J. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.061929 · Cited by 364
Self-citationHaack, T. B., Hogarth, P., Kruer, M. C., Gregory, A., Wieland, T., Schwarzmayr, T., Graf, E., Sanford, L., Meyer, E., Kara, E., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.10.019 · Cited by 360
Self-citationParamagnetic metal scavenging by melanin: MR imaging.
Enochs, W. S., Petherick, P., Bogdanova, A., Möhr, U., & Weissleder, R. (1997) · Radiology · doi:10.1148/radiology.204.2.9240529 · Cited by 289
Zhang, W., Phillips, K., Wielgus, A. R., Liu, J., Albertini, A., Zucca, F. A., Faust, R., Qian, S. Y., Miller, D. S., Chignell, C. F., et al. (2011) · Neurotoxicity Research · doi:10.1007/s12640-009-9140-z · Cited by 257
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Meyerink, B. L., Karia, K. S., Rechtzigel, M. J., Patthi, P. R., Edwards, A. C., Howard, J. M., Aaseng, E. R., Aftab, S., Weimer, J. M., & Pilaz, L. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1545004 · Cited by 1
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森貞直哉, 常石, 秀., 和裕, 田., 隆三郎, 八., 西山, 将., 豊嶋, 大., 卓, 中., 泰弘, 竹., 哲, 高., & 一誠, 飯. (2016) · 脳と発達 · doi:10.11251/ojjscn.48.209 · Cited by 1
Diagnosing neurodegeneration with brain iron accumulation before iron starts to accumulate
Hoogwijs, I. (2019) · Journal of the International Child Neurology Association · doi:10.17724/jicna.2018.117 · Cited by 1
Molecular basis of movement disorders
MacIver, C., Morgan, D., & Peall, K. J. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-809356-6.00027-7 · Cited by 1
Neuroaxonal Dystrophy/Neurodegeneration with Brain Iron Accumulation
Li, A., Wiethoff, S., Arber, C., Houlden, H., Révész, T., & Holton, J. L. (2018) · Wiley eBooks · doi:10.1002/9781119013112.ch38 · Cited by 1
Self-citationNeurodegeneration with Brain Iron Accumulation: and Management
Hogarth, P. (2015)
Self-citationOther neurogenerative conditions III
Vidal, R., & Ghetti, B. F. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781107588660.015
Aging-Related Diseases and Autophagy
Arısan, E. D., Yerlikaya, P. O., Gürkan, A. Ç., & Palavan-Ünsal, N. (2016) · InTech eBooks · doi:10.5772/64540
Asim K. Bag, Lázaro Luís Faria do Amaral
Byan-Parker, S. (2016) · Cambridge University Press eBooks · doi:10.1017/9781316105139.005
Neurodegeneration with Brain Iron Accumulation, Wilson Disease, and Manganism
McNeill, A. (2017) · Neurodegeneration · doi:10.1002/9781118661895.ch26
Ceballos-Baumann, A. (2018) · Nervenheilkunde · doi:10.1055/s-0038-1642089
Contratación por internet: la revolución jurídica del siglo XXI
Belupu, H. Ñ. (2002) · Advocatus · doi:10.26439/advocatus2002.n006.2348
Imaging in Movement Disorder Phenomenology
Frucht, S. J., & Termsarasab, P. (2020) · Springer eBooks · doi:10.1007/978-3-030-36975-0_17
Self-citationPerunova, N. Y., Bobylova, M. Y., & Михайловна, П. Т. (2020) · Russian Journal of Child Neurology · doi:10.17650/2073-8803-2020-15-1-47-61
D’Amico, A., Romano, A., Parrini, E., Ugga, L., & Terrone, G. (2021) · Neurological Sciences · doi:10.1007/s10072-021-05149-7
WDR45 Gene and Its Role in Pediatric Epilepsies
Filosco, F., Billone, S., Collotta, A. D., Timpanaro, T., Tosto, M., Falsaperla, R., Marino, S., Zanghì, A., & Praticò, A. D. (2021) · Journal of Pediatric Neurology · doi:10.1055/s-0041-1727174
Infantile Developmental Delay Caused by Pathogenic Mutation in WDR45 Gene and Literature ReviewPreprint
Cao, Q., Wang, H., & Huo, L. (2021) · Research Square · doi:10.21203/rs.3.rs-964834/v1
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Diagnosis of Neurogenetic Disorders: Contribution of Next Generation Sequencing and Deep Phenotyping
McNeill, A. (2019) · MDPI eBooks · doi:10.3390/books978-3-03921-611-6
Hawkes, C. H., Sethi, K. D., & Swift, T. R. (2016) · doi:10.1093/med/9780199361953.003.0008
Hawkes, C. H., Sethi, K. D., & Swift, T. R. (2019) · doi:10.1093/med/9780190930868.003.0008
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Chiapparini, L., & Zorzi, G. S. (2022) · American Journal of Neuroradiology · doi:10.3174/ajnr.a7723
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Mansour, M. A., Moawad, Y., & Ali, H. M. (2023) · eNeurologicalSci · doi:10.1016/j.ensci.2023.100469
Cardiac glycosides restore autophagy flux in an iPSC-derived neuronal model of WDR45 deficiencyPreprint
Papandreou, A., Singh, N., Gianfrancesco, L., Budinger, D., Barwick, K. E., Agrotis, A., Luft, C., Shao, Y., Lenaerts, A., Gregory, A., et al. (2024) · eLife · doi:10.7554/elife.91725
Self-citationCardiac glycosides restore autophagy flux in an iPSC-derived neuronal model of WDR45 deficiencyPreprint
Papandreou, A., Singh, N., Gianfrancesco, L., Budinger, D., Barwick, K. E., Agrotis, A., Luft, C., Shao, Y., Lenaerts, A., Gregory, A., et al. (2024) · eLife · doi:10.7554/elife.91725.1
Self-citationCarisi, M. C., Shamber, C. E., Bishop, M., Sangster, M., Chandrachud, U., Meyerink, B. L., Pilaz, L., & Grishchuk, Y. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.18.599588
DOVBONOS, T. A., Svystilnyk, V. O., Krylova, V. Y., & Simonenko, G. G. (2024) · INTERNATIONAL NEUROLOGICAL JOURNAL · doi:10.22141/2224-0713.20.7.2024.1117
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Koshy, K. G., Fasaludeen, A., & Menon, R. N. (2025) · Neurology India · doi:10.4103/neurol-india.neurol-india-d-24-00489
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Hawkes, C. H., Balint, B., & Biller, J. (2025) · doi:10.1093/med/9780197699461.003.0009
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Monje, M. H. G., Vittal, P., Sarmiento, I. J. K., Kinsley, L. M., Krainc, D., & Mencacci, N. E. (2025) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.70313
Özata, G., Wise, R. M., Cardona‐Alberich, A., Mayeen, N. F., Müller, S. A., Lichtenthaler, S. F., Zecca, L., & Burbulla, L. F. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.04.668126
Süsgün, S., Kizek, Ö., İşerı̇, S. A. U., Kamacı, İ., Elmalı, A. D., İşçen, P., Guzel, B. G., Çakmaklı, G. Y., Elibol, B., Donmez, B., et al. (2025) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.70220
Yin, T., Dong, P., Shi, X., Huang, Z., Guo, X., Zhou, W., & Wang, H. (2025) · Stem Cell Research · doi:10.1016/j.scr.2025.103860
Lopes, S., Ribeiro, M., Mesquita, I., Carrilho, I., Garrido, C., Santos, M., Figueiroa, S., Martins, J., Cardoso, J., & Temudo, T. P. (2025) · Neurology Perspectives · doi:10.1016/j.neurop.2025.100211
Romero-González, A., Reche-López, D., Álvarez-Córdoba, M., Suárez-Carrillo, A., Cilleros-Holgado, P., Piñero-Pérez, R., Gómez-Fernández, D., Romero-Domínguez, J. M., López-Cabrera, A., & Sánchez-Alcázar, J. A. (2025) · International review of cytology · doi:10.1016/bs.ircmb.2025.10.004
Ahmad, F., Sandal, S., Gadgil, P., Shah, S., Shah, A., Angi, M., Chaudhary, P. S., Chaudhary, S. A., & Arora, N. (2025) · Gene Reports · doi:10.1016/j.genrep.2025.102410
Other neurogenerative conditions IV
Ferrer, I. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781107588660.016
Wang, P., Shao, Y., Al-Nusaif, M., Zhang, J., Yang, H., Yang, Y., Kim, K., Li, S., Liu, C., Cai, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26943114
Wang, P., Shao, Y., Al-Nusaif, M., Zhang, J., Yang, H., Yang, Y., Kim, K., Li, S., Liu, C., Cai, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26943117
Wang, P., Shao, Y., Al-Nusaif, M., Zhang, J., Yang, H., Yang, Y., Kim, K., Li, S., Liu, C., Cai, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26943120
Xiong, Q., Sun, H., Wang, Y., Xu, Q., Zhang, Y., Xu, M., Zhao, Z., Li, P., & Wu, C. (2024) · Figshare · doi:10.6084/m9.figshare.25495204
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Michelson, M., Zahavi, A., Zobok, T., Yosovich, K., Blumkin, L., Maharshak, I., Lev, D., Girshevitz, O., & Goldenberg‐Cohen, N. (2026) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-026-04315-4
Elevated Plasma Phospho‐Tau217 in Beta‐Propeller Protein‐Associated Neurodegeneration
Lee, J., & Kim, Y. S. (2026) · Movement Disorders · doi:10.1002/mds.70405
Kai, T., Tominaga, K., Matsunaga, A., Shimizu, H., Iwama, K., & Ishizawa, K. (2026) · Reports — Medical Cases Images and Videos · doi:10.3390/reports9030209
Functional Homology of WIPI4 and Atg18 Enables WDR45 Variant Interpretation for BPAN Diagnosis
Morin, V., Durand, C. M., Angelini, C., Stévanin, G., Fergelot, P., Goizet, C., Coupry, I., & Lasserre, J.-P. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27157054
Kumar, N., Kumari, S., Mehta, S., Singh, J., Joshi, D., & Gupta, R. (2026) · Sleep and Vigilance · doi:10.1007/s41782-026-00367-5
Sohn, J. E., Lee, K., Kim, Y., & Lee, S.-H. (2026) · Journal of Clinical Neurology · doi:10.3988/jcn.2026.0094
Genetic and neuropathological study of primary and secondary dystonic syndromes
Paudel, R. (2015) · UCL Discovery (University College London)
Metadata
- Authors
- Hayflick, S. J., Kruer, M. C., Gregory, A., Haack, T. B., Kurian, M. A., Houlden, H. H., Anderson, J., Boddaert, N., Sanford, L., Harik, S. I., Dandu, V. H., Nardocci, N., Zorzi, G., Dunaway, T., Tarnopolsky, M., Skinner, S., Holden, K. R., Frucht, S., Hanspal, E., Schrander-Stumpel, C., Mignot, C., Héron, D., Saunders, D. E., Kaminska, M., Lin, J.-P., Lascelles, K., Cuno, S. M., Meyer, E., Garavaglia, B., Bhatia, K., de Silva, R., Crisp, S., Lunt, P., Carey, M., Hardy, J., Meitinger, T., Prokisch, H., & Hogarth, P.
- Affiliations
- Oregon Health & Science University (US)
- Helmholtz Munich (DE)
- Great Ormond Street Hospital (GB)
- Hôpital Necker-Enfants Malades (FR)
- UCL Queen Square Institute of Neurology (GB)
- McMaster University Medical Centre (CA)
- Albany Medical College (US)
- Pitié-Salpêtrière Hospital (FR)
- University of South Dakota (US)
- Queen's Hospital (GB)
- University Hospitals Bristol NHS Foundation Trust (GB)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Corresponding author
- Hayflick, Susan J.
- ORCID
- Hayflick, Susan J.
- Kruer, Michael C.
- Gregory, Allison
- Haack, Tobias B.
- Kurian, Manju A.
- Houlden, Henry H.
- Anderson, James
- Boddaert, Nathalie
- Sanford, Lynn
- Nardocci, Nardo
- Zorzi, Giovanna
- Tarnopolsky, Mark
- Skinner, Steven
- Frucht, Steven
- Mignot, Cyril
- Héron, Delphine
- Saunders, Dawn E.
- Kaminska, Margaret
- Lin, Jean-Pierre
- Lascelles, Karine
- Meyer, Esther
- Garavaglia, Barbara
- Bhatia, Kailash
- Crisp, Sarah
- Lunt, Peter
- Hardy, John
- Meitinger, Thomas
- Prokisch, Holger
- Hogarth, Penelope
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-05-17
- Volume
- 136
- Issue
- 6
- Pages
- 1708-1717
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3673459
- OpenAlex
- W2159322366
- Cited by
- 250
- References
- 23
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 16 · 2023: 12 · 2022: 16 · 2021: 21 · 2020: 21 · 2019: 20 · 2018: 20 · 2017: 27 · 2016: 16 · 2015: 30 · 2014: 17 · 2013: 6
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Portal (King's College London) (publishedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Parkinson's Disease Foundation
- Dystonia Medical Research Foundation
- Child Neurology Foundation
- University of Dundee
- NBIA Disorders Association
- Wellcome Trust (FP7/2007–2013)
- Action Medical Research
- Brain Research Trust
- European Commission (2007–2013, FP7 2007-2013, 261123, 277984, FP7/2007)
- Bundesministerium für Bildung und Forschung (01GR0804-4, SysMBo 0315494A, 01GR0804, 01GM0867, 0315494A)
- National Institutes of Health (277984, UL1TR000128, FP7/2007-2013, HEALTH-F2-2011, RR024140)
- Oregon Clinical and Translational Research Institute (UL1RR024140, RR024140, UL1 RR024140 NCRR)
- Medical Research Council (FP7/20072013, MR/J004758/1)
- National Institute of Neurological Disorders and Stroke (K08NS083739)
- National Center for Research Resources (UL1 RR024140 NCRR, UL1RR024140, RR024140)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- beta-propeller protein-associated neurodegeneration, WDR45, neurodegeneration with brain iron accumulation, X-linked dominant disorder, de novo mutations, beta-propeller proteins, autophagy, basal ganglia iron accumulation, parkinsonism, dystonia, dementia, developmental delay, levodopa response, dyskinesia, substantia nigra, globus pallidus, natural history (disease)
- MeSH terms
- Adolescent, Adult, Brain, Carrier Proteins, Female, Humans, Iron, Male, Middle Aged, Mutation, Cohort Studies, Neurodegenerative Diseases, Genetic Diseases, X-Linked, Young Adult
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