Genetic Analysis of Inherited Leukodystrophies: Genotype-Phenotype Correlations in the CSF1R Gene

Rita Guerreiro, Eleanna Kara, Isabelle Le Ber, Jose Bras, Jonathan D. Rohrer, Ricardo Taipa, Tammaryn Lashley, Céline Dupuits, Nicole Gurunlian, Fanny Mochel, Jason D. Warren, Didier Hannequin, Frédéric Sedel, Christel Depienne, Agnès Camuzat, Véronique Golfier, Foucaud Du Boisguéheneuc, Lucia Schottlaender, Nick C. Fox, Jonathan Beck, Simon Mead, Martin N. Rossor, John Hardy, Tamas Revesz, Alexis Brice, Henry Houlden

The leukodystrophies comprise a clinically and genetically heterogeneous group of progressive hereditary neurological disorders mainly affecting the myelin in the central nervous system. Their onset is variable from childhood to adulthood and presentation can be with a variety of clinical features that include mainly for adult-onset cases cognitive decline, seizures, parkinsonism, muscle weakness, neuropathy, spastic paraplegia, personality/behavioral problems, and dystonia. Recently, Rademakers and colleagues identified mutations in the CSF1R gene as the cause of hereditary diffuse leukoencephalopathy with spheroids (HDLS), offering the possibility for an in-life diagnosis. The detection of mutations in this gene in cases diagnosed with different clinical entities further demonstrated the difficulties in the clinical diagnosis of HDLS.