PURPOSE OF REVIEW: There is growing interest in disorders involved in ectopic mineralization. Fahr disease or idiopathic basal ganglia calcification can serve as a model for ectopic mineralization in the basal ganglia, which is fairly common in the general population. In this review, we will focus on causative gene mutations and corresponding pathophysiologic pathways in Fahr disease. RECENT FINDINGS: Patients with Fahr disease have a variability of symptoms, such as movement disorders, psychiatric signs, and cognitive impairment, but can also be asymptomatic. Fahr disease is mostly autosomal dominant inherited, and there are mutations found in 4 causative genes. Mutations in SLC20A2 and XPR1 lead to a disrupted phosphate metabolism involving brain-specific inorganic phosphate transporters. Mutations in PDGFB and PDGFRB are associated with disrupted blood-brain barrier integrity and dysfunctional pericyte maintenance. In addition, the MYORG gene has recently been discovered to be involved in the autosomal recessive inheritance of Fahr. SUMMARY: Knowledge about the mutations and corresponding pathways may expose therapeutic opportunities for patients with Fahr disease and vascular calcifications in the brain in general.
PURPOSE OF REVIEW: There is growing interest in disorders involved in ectopic mineralization. Fahr disease or idiopathic basal ganglia calcification can serve as a model for ectopic mineralization in the basal ganglia, which is fairly common in the general population. In this review, we will focus on causative gene mutations and corresponding pathophysiologic pathways in Fahr disease. RECENT FINDINGS: Patients with Fahr disease have a variability of symptoms, such as movement disorders, psychiatric signs, and cognitive impairment, but can also be asymptomatic. Fahr disease is mostly autosomal dominant inherited, and there are mutations found in 4 causative genes. Mutations in SLC20A2 and XPR1 lead to a disrupted phosphate metabolism involving brain-specific inorganic phosphate transporters. Mutations in PDGFB and PDGFRB are associated with disrupted blood-brain barrier integrity and dysfunctional pericyte maintenance. In addition, the MYORG gene has recently been discovered to be involved in the autosomal recessive inheritance of Fahr. SUMMARY: Knowledge about the mutations and corresponding pathways may expose therapeutic opportunities for patients with Fahr disease and vascular calcifications in the brain in general.
Authors: Annika Keller; Ana Westenberger; Maria J Sobrido; Maria García-Murias; Aloysius Domingo; Renee L Sears; Roberta R Lemos; Andres Ordoñez-Ugalde; Gael Nicolas; José E Gomes da Cunha; Elisabeth J Rushing; Michael Hugelshofer; Moritz C Wurnig; Andres Kaech; Regina Reimann; Katja Lohmann; Valerija Dobričić; Angel Carracedo; Igor Petrović; Janis M Miyasaki; Irina Abakumova; Maarja Andaloussi Mäe; Elisabeth Raschperger; Mayana Zatz; Katja Zschiedrich; Jörg Klepper; Elizabeth Spiteri; Jose M Prieto; Inmaculada Navas; Michael Preuss; Carmen Dering; Milena Janković; Martin Paucar; Per Svenningsson; Kioomars Saliminejad; Hamid R K Khorshid; Ivana Novaković; Adriano Aguzzi; Andreas Boss; Isabelle Le Ber; Gilles Defer; Didier Hannequin; Vladimir S Kostić; Dominique Campion; Daniel H Geschwind; Giovanni Coppola; Christer Betsholtz; Christine Klein; Joao R M Oliveira Journal: Nat Genet Date: 2013-08-04 Impact factor: 38.330
Authors: Shira G Ziegler; Carlos R Ferreira; Elena Gallo MacFarlane; Ryan C Riddle; Ryan E Tomlinson; Emily Y Chew; Ludovic Martin; Chen-Ting Ma; Eduard Sergienko; Anthony B Pinkerton; José Luis Millán; William A Gahl; Harry C Dietz Journal: Sci Transl Med Date: 2017-06-07 Impact factor: 17.956
Authors: A Li; R Paudel; R Johnson; R Courtney; A J Lees; J L Holton; J Hardy; T Revesz; H Houlden Journal: Neuropathol Appl Neurobiol Date: 2013-02 Impact factor: 8.090