Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification
| Autor: | Jon E. Berner, Olga Carmona, Bala V. Manyam, Martin Paucar, Henry Brodaty, Giovanni Coppola, Henry L. Paulson, Milena Jankovic, Melissa K. Maisenbacher, John C. Adair, Janice M. Fullerton, Alden Y. Huang, Renee L. Sears, Serge Jaumà, Joanna C. Jen, Joerg Klepper, John L. Goudreau, Jerrold L. Vitek, Daniel H. Geschwind, Beatriz Quintáns, Elizabeth Spiteri, Witoon Mitarnun, Per Svenningsson, Charles A. Williams, Mayana Zatz, Sheila A Simpson, Daniel García-Estevez, Philip B. Mitchell, João Ricardo Mendes de Oliveira, Vladimir S. Kostic, Sandy Chan Hsu, Peter R. Schofield, Jill Goldman, Brent L. Fogel, R. R. Lemos, Michele Yang, Catherine Mamah, Ivana Novakovic, Lisette Nevarez, Pietro Mazzoni, Z. Miedzybrodzka, Agnès Linglart, Paul J. Tuite, Kerrie D. Pierce, Suppachok Wetchaphanphesat, María Jesús Sobrido, Jennifer Mueller, Anthony E. Lang, Matthew Bower, Valerija Dobricic, Suppachok Kirdlarp, Suellen Hopfer |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male media_common.quotation_subject Nonsense DNA Mutational Analysis Molecular Sequence Data Basal ganglia calcification Disease Biology Bioinformatics Ganglis basals Models Biological Linkage Disequilibrium Cohort Studies Cellular and Molecular Neuroscience Basal Ganglia Diseases Genetics Missense mutation Humans Medical history Family Amino Acid Sequence Gene Genetics (clinical) media_common Aged Retrospective Studies Genetic heterogeneity Sodium-Phosphate Cotransporter Proteins Type III Calcinosis Neurodegenerative Diseases Middle Aged GENÉTICA MÉDICA Phenotype Mutation Basal ganglia Female Genètica |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation. |
| Databáze: | OpenAIRE |
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