title: Fahr's disease linked to a novel SLC20A2 gene mutation manifesting with dynamic aphasia.
abstract: BACKGROUND
  Idiopathic basal ganglia calcification (IBGC), also known as Fahr's disease, is a rare disorder characterized by widespread cerebral calcifications, an autosomal dominant pattern of inheritance and clinical and genetic heterogeneity. The recently identified IBGC gene, SLC20A2, encodes for type III sodium-dependent phosphate transporter 2 and its loss-of-function mutations may lead to the regional accumulation of inorganic phosphate in the brain, causing calcium phosphate deposition.
  
  
  OBJECTIVE
  To describe the clinical, neuroimaging and genetic findings in an Italian family with IBGC.
  
  
  METHODS
  The family members underwent clinical and radiological examination in order to diagnose IBGC according to standard criteria and screening for SLC20A2 gene mutations. The affected subjects also underwent neuropsychological longitudinal assessments and functional neuroimaging investigations.
  
  
  RESULTS
  The 2 affected family members harbored a novel missense mutation, G1618A, in the SLC20A2 gene, leading to gly540-to-arg (G540R) substitution in a highly conserved residue. This is the first SLC20A2 gene mutation associated with familial IBGC reported in the Italian population and is damaging according to all prediction programs. In the index case we observed a fair correlation between cortical areas with no calcifications but with significant hypometabolism at [18F]FDG-PET (inferior frontal premotor cortex) and the neuropsychological picture dominated by dynamic aphasia and buccofacial apraxia.
  
  
  CONCLUSIONS
  These findings expand the catalog of SLC20A2 mutations identified to date and add dynamic aphasia to the spectrum of neuropsychological deficits reported in IBGC, supporting the use of functional neuroimaging studies for better investigation of genotype-phenotype correlations.
authors.affiliation: Department of Neurology, San Gerardo Hospital, Milan Center for Neuroscience, Monza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Brighina
authors.forename: Enrico
authors.initials: E
authors.lastname: Saracchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferri
authors.forename: Monica
authors.initials: M
authors.lastname: Gagliardi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarantino
authors.forename: Sabrina
authors.initials: S
authors.lastname: Morzenti
authors.forename: Monica
authors.initials: M
authors.lastname: Musarra
authors.forename: Mirko
authors.initials: M
authors.lastname: Patassini
authors.forename: Grazia
authors.initials: G
authors.lastname: Annesi
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrarese
mesh_terms: D000368:Aged; D001037:Aphasia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D001480:Basal Ganglia Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000473:pathology; D002114:Calcinosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D020125:Mutation, Missense; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D010375:Pedigree; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics*; D055815:Young Adult
chemical_list: C493589:SLC20A2 protein, human; D050611:Sodium-Phosphate Cotransporter Proteins, Type III