title: Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Caused by a Novel R782G Mutation in CSF1R.
abstract: We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration with axonal swellings and pigmented macrophages. The few recently reported families with CSF1R mutations had been previously labelled "hereditary diffuse leukencephalopathy with axonal spheroids" (HDLS) and "pigmentary orthochromatic leukodystrophy" (POLD), disorders which now appear to form a disease continuum. The term "adult-onset leukoencephalopathy with axonal spheroids and pigmented glia" (ALSP) has been proposed to encompass this spectrum. As CSF1R regulates microglia this mutation implies that dysregulation of microglia is the primary cause of the disease.
authors.affiliation: 1] Wessex Clinical Genetics Services, University Hospital Southampton NHS Foundation Trust, UK [2] Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, UK. Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Foulds
authors.affiliation: Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, UK. Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, UK.
authors.forename: Reuben J
authors.initials: RJ
authors.lastname: Pengelly
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Hammans
authors.affiliation: Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK.
authors.forename: James A R
authors.initials: JA
authors.lastname: Nicoll
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.affiliation: Department of Radiology, University Hospital Southampton NHS Foundation Trust, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Ditchfield
authors.affiliation: Wessex Clinical Genetics Services, University Hospital Southampton NHS Foundation Trust, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Beck
authors.affiliation: Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, UK. Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ennis
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology*; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics; D008264:Macrophages / Q000166:cytology; D008297:Male; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000473:pathology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*; D066127:White Matter / Q000473:pathology*
chemical_list: D016186:Receptor, Macrophage Colony-Stimulating Factor