title: A novel mutation in the CSF1R gene causes a variable leukoencephalopathy with spheroids.
abstract: Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids is a neurodegenerative disease associated with mutations in the colony-stimulating factor 1 receptor gene (CSF1R). A 44-year-old woman with a 7-year history of depression presented with neurological signs and a recent cognitive decline. The diagnosis of hereditary diffuse leukoencephalopathy with neuroaxonal spheroids was suspected based on the findings of a predominant frontal leukoencephalopathy and neuroaxonal spheroids on brain biopsy. She shares with her mother a novel CSF1R exon 18 missense mutation (c.2350G > A; p.V784M). The mother has a long-standing bipolar disorder and mild multifocal white matter abnormalities in her 70s. This is the first report of hereditary diffuse leukoencephalopathy with neuroaxonal spheroids due to this novel CSF1R missense mutation. Our report suggests that either marked intrafamilial variability or incomplete penetrance can be associated with CSF1R mutations. The observation of a small bone cyst in our patient supports the hypothesis that hereditary diffuse leukoencephalopathy with neuroaxonal spheroids and polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy may belong to a spectrum of overlapping phenotypes.
authors.affiliation: Laboratory of Neurogenetics of Motion, Montreal Neurological Institute, McGill University, 3801 University Street, Room 622, Montreal, QC, H3A 2B4, Canada, roberta.lapiana@mail.mcgill.ca.
authors.forename: Roberta
authors.initials: R
authors.lastname: La Piana
authors.forename: Alina
authors.initials: A
authors.lastname: Webber
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Guiot
authors.forename: Maria
authors.initials: M
authors.lastname: Del Pilar Cortes
authors.forename: Bernard
authors.initials: B
authors.lastname: Brais
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology; D001845:Bone Cysts / Q000150:complications / Q000000981:diagnostic imaging; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D056784:Leukoencephalopathies / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D011859:Radiography; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*
chemical_list: D016186:Receptor, Macrophage Colony-Stimulating Factor