Gert Van Goethem1, John H Livingston2, Daniel Warren3, Anthony J Oojageer4, Gillian I Rice4, Yanick J Crow5. 1. Department of Neurology, University Hospital of Antwerpen (UZA), Antwerpen, Belgium. 2. Department of Paediatric Neurology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. 3. Department of Neuroradiology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. 4. Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences; Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom. 5. Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences; Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom; INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Hôpital Necker, Paris, France; Paris Descartes University, Paris, France. Electronic address: yanickcrow@mac.com.
Abstract
BACKGROUND: Beta-propeller protein-associated neurodegeneration is a newly described X-linked dominant condition due to heterozygous mutations in WDR45. The condition is associated with characteristic changes on brain magnetic resonance imaging. Previous literature relating to this disorder has not specifically referred to intracranial calcification. METHODS: A female patient presented with significant developmental delay in early childhood and subsequently demonstrated neurodegeneration with progressive dystonia and dementia in her third decade. Brain magnetic resonance imaging revealed low signal in the substantia nigra and both globus pallidi on T2-weighted imaging, with no eye-of-the-tiger sign. Computed tomography revealed bilateral dense calcification of the globus pallidus. We performed Sanger sequencing of the WDR45 gene in the patient and her parents. RESULTS: We identified a heterozygous c.488del C p.Pro163Argfs*34 variant in exon 8 of WDR45. Neither parent carried the same mutation, indicating that the molecular change had occurred de novo. CONCLUSIONS: Although the characteristic features of beta-propeller protein-associated neurodegeneration were present in our patient, the observation of basal ganglia calcification was considered atypical. Previous descriptions of basal ganglia calcification in individuals with neuronal brain iron accumulation led us to review the frequency of calcification in these disorders.
BACKGROUND: Beta-propeller protein-associated neurodegeneration is a newly described X-linked dominant condition due to heterozygous mutations in WDR45. The condition is associated with characteristic changes on brain magnetic resonance imaging. Previous literature relating to this disorder has not specifically referred to intracranial calcification. METHODS: A female patient presented with significant developmental delay in early childhood and subsequently demonstrated neurodegeneration with progressive dystonia and dementia in her third decade. Brain magnetic resonance imaging revealed low signal in the substantia nigra and both globus pallidi on T2-weighted imaging, with no eye-of-the-tiger sign. Computed tomography revealed bilateral dense calcification of the globus pallidus. We performed Sanger sequencing of the WDR45 gene in the patient and her parents. RESULTS: We identified a heterozygous c.488del C p.Pro163Argfs*34 variant in exon 8 of WDR45. Neither parent carried the same mutation, indicating that the molecular change had occurred de novo. CONCLUSIONS: Although the characteristic features of beta-propeller protein-associated neurodegeneration were present in our patient, the observation of basal ganglia calcification was considered atypical. Previous descriptions of basal ganglia calcification in individuals with neuronal brain iron accumulation led us to review the frequency of calcification in these disorders.
Authors: Darius Ebrahimi-Fakhari; Afshin Saffari; Lara Wahlster; Jenny Lu; Susan Byrne; Georg F Hoffmann; Heinz Jungbluth; Mustafa Sahin Journal: Brain Date: 2015-12-29 Impact factor: 13.501
Authors: Yuri A Zarate; Julie R Jones; Melanie A Jones; Francisca Millan; Jane Juusola; Annette Vertino-Bell; G Bradley Schaefer; Michael C Kruer Journal: Eur J Hum Genet Date: 2015-11-18 Impact factor: 4.246