title: Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): update on molecular genetics.
abstract: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disease characterized by giant neuroaxonal swellings (spheroids) within the cerebral white matter (WM). Symptoms are variable and can include cognitive, mental and motor dysfunctions. Patients carry mutations in the protein kinase domain of the colony-stimulating factor 1 receptor (CSF1R) which is a tyrosine kinase receptor essential for microglia development. To date, more than 50 pathogenic variants have been reported in patients with HDLS, including missense, frameshift and non-sense mutations, but also deletions and splice-site mutations, all located in the intracellular tyrosine kinase domain, encoded by exons 12-22. The aim of this paper is to review the literature data about the molecular genetic pattern of HDLS.
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Stabile
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Taglia
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.|Unit Clinical Neurology and Neurometabolic Diseases, Azienda Ospedaliera Universitaria Senese, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Battisti
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. federico@unisi.it.|Unit Clinical Neurology and Neurometabolic Diseases, Azienda Ospedaliera Universitaria Senese, Viale Bracci 2, 53100, Siena, Italy. federico@unisi.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics*; D008967:Molecular Biology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics
chemical_list: D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: CSF-1R mutations; HDLS; Leukoencephalopathy; Spheroids