Supplementary Material for: Fahr's Disease Linked to a Novel <b><i>SLC20A2 </i></b>Gene Mutation Manifesting with Dynamic Aphasia
2014-09-25T00:00:00Z (GMT) by
<b><i>Background:</i></b> 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, <i>SLC20A2,</i> 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. <b><i>Objective:</i></b> To describe the clinical, neuroimaging and genetic findings in an Italian family with IBGC. <b><i>Methods:</i></b> The family members underwent clinical and radiological examination in order to diagnose IBGC according to standard criteria and screening for <i>SLC20A2</i> gene mutations. The affected subjects also underwent neuropsychological longitudinal assessments and functional neuroimaging investigations. <b><i>Results:</i></b> The 2 affected family members harbored a novel missense mutation, G1618A, in the <i>SLC20A2</i> gene, leading to gly540-to-arg (G540R) substitution in a highly conserved residue. This is the first <i>SLC20A2 </i>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. <b><i>Conclusion:</i></b> These findings expand the catalog of <i>SLC20A2</i> 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.