@article{d47b69ce2c83480a8c6b30cd8c30810c,
title = "Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA",
abstract = "Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic disorders characterized by abnormal iron deposition in the basal ganglia. We report that de novo mutations in WDR45, a gene located at Xp11.23 and encoding a beta-propeller scaffold protein with a putative role in autophagy, cause a distinctive NBIA phenotype. The clinical features include early-onset global developmental delay and further neurological deterioration (parkinsonism, dystonia, and dementia developing by early adulthood). Brain MRI revealed evidence of iron deposition in the substantia nigra and globus pallidus. Males and females are phenotypically similar, an observation that might be explained by somatic mosaicism in surviving males and germline or somatic mutations in females, as well as skewing of X chromosome inactivation. This clinically recognizable disorder is among the more common forms of NBIA, and we suggest that it be named accordingly as beta-propeller protein-associated neurodegeneration.",
author = "Haack, {Tobias B.} and Penelope Hogarth and Kruer, {Michael C.} and Allison Gregory and Thomas Wieland and Thomas Schwarzmayr and Elisabeth Graf and Lynn Sanford and Esther Meyer and Eleanna Kara and Cuno, {Stephan M.} and Harik, {Sami I.} and Dandu, {Vasuki H.} and Nardo Nardocci and Giovanna Zorzi and Todd Dunaway and Mark Tarnopolsky and Steven Skinner and Steven Frucht and Era Hanspal and Connie Schrander-Stumpel and Delphine H{\'e}ron and Cyril Mignot and Barbara Garavaglia and Kailash Bhatia and John Hardy and Strom, {Tim M.} and Nathalie Boddaert and Houlden, {Henry H.} and Kurian, {Manju A.} and Thomas Meitinger and Holger Prokisch and Hayflick, {Susan J.}",
note = "Funding Information: The authors gratefully acknowledge the study participants and families, as well as the support of our advocacy partners: the NBIA Disorders Association, Hoffnungsbaum e.V., and Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro. This work was funded by the NBIA Disorders Association and was made possible with support from the Oregon Clinical and Translational Research Institute (UL1 RR024140 NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. P.H., N.N., T.M., H.P., and S.J.H. participate in the TIRCON consortium (European Commission Seventh Framework Program, FP7/2007-2013, HEALTH-F2-2011, grant agreement 277984). We thank Evelyn Botz and Carola Fischer for technical support. T.M. and H.P. were supported by the German Federal Ministry of Education and Research (Systems Biology of Metabotypes grant SysMBo 0315494A) and the German Network for Mitochondrial Disorders (mitoNET 01GM0867). T.M. and T.M.S. were supported by the European Commission Seventh Framework Program (N. 261123), Genetic European Variation in Disease Consortium, and German Ministry for Education and Research (01GR0804-4). M.C.K. receives support from the American Academy of Neurology and American Philosophical Society. We thank the Cell line and DNA bank of pediatric movement disorders of the Telethon Genetic Biobank Network (GTB07001). M.A.K.{\textquoteright}s research is supported by Action Medical Research. We thank the UK Parkinson{\textquoteright}s Disease Consortium, University College London Institute of Neurology, University of Sheffield, University of Dundee, Medical Research Council, Parkinson{\textquoteright}s Disease Foundation, Dystonia Medical Research Foundation, and Brain Research Trust. ",
year = "2012",
month = dec,
day = "7",
doi = "10.1016/j.ajhg.2012.10.019",
language = "English (US)",
volume = "91",
pages = "1144--1149",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "6",
}