Abstract
Variants in the WD repeat 45 (WDR45) gene in human Xp11.23 have recently been identified in patients suffering from neurodegeneration with brain iron accumulation, a genetically and phenotypically heterogeneous condition. WDR45 variants cause a childhood-onset encephalopathy accompanied by neurodegeneration in adulthood and iron accumulation in the basal ganglia. They have been almost exclusively found in females, and male lethality was suggested. Here we describe a male patient suffering from a severe and early neurological phenotype, initially presenting early-onset epileptic spasms in clusters associated with an abnormal interictal electroencephalography showing slow background activity, large amplitude asynchronous spikes and abnormal neurological development. This patient is a carrier of a 19.9-kb microdeletion in Xp11.23 containing three genes, including WDR45. These findings reveal that males with WDR45 deletions are viable, and can present with early-onset epileptic encephalopathy without brain iron accumulation.
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Acknowledgements
We thank the patient and his family for their participation in this study. This work was supported by Programme Hospitalier de Recherche Clinique 2011, Inserm and Aix Marseille University. We thank the Centre de Ressources Biologiques of La Timone Children's Hospital (Karine Bertaux, Cécile Mouradian and Andrée Robaglia-Schlupp) for assistance with the samples used in this study.
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Abidi, A., Mignon-Ravix, C., Cacciagli, P. et al. Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient. Eur J Hum Genet 24, 615–618 (2016). https://doi.org/10.1038/ejhg.2015.159
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DOI: https://doi.org/10.1038/ejhg.2015.159
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