• David S Lynch, Zane Jaunmuktane, Una-Marie Sheerin, Rahul Phadke, Sebastian Brandner, Ionnis Milonas, Andrew Dean, Nin Bajaj, Nuala McNicholas, Daniel Costello, Simon Cronin, Chris McGuigan, Martin Rossor, Nick Fox, Elaine Murphy, Jeremy Chataway, and Henry Houlden.
• Department of Molecular Neuroscience, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, Queen Square, London, UK The Leonard Wolfson Experimental Neurology Centre, The National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London UK.
• J. Neurol. Neurosurg. Psychiatr. 2016 May 1; 87 (5): 512-9.

BackgroundHereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene.MethodsIn this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause.ResultsFive pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations.ConclusionWe estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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