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Comprehensive genetic screening of early-onset dementia patients in an Austrian cohort-suggesting new disease-contributing genes.
Silvaieh, Sara; König, Theresa; Wurm, Raphael; Parvizi, Tandis; Berger-Sieczkowski, Evelyn; Goeschl, Stella; Hotzy, Christoph; Wagner, Matias; Berutti, Riccardo; Sammler, Esther; Stögmann, Elisabeth; Zimprich, Alexander.
Afiliación
  • Silvaieh S; Department of Neurology, Medical University of Vienna, Vienna, Austria.
  • König T; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
  • Wurm R; Department of Neurology, Medical University of Vienna, Vienna, Austria.
  • Parvizi T; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
  • Berger-Sieczkowski E; Department of Neurology, Medical University of Vienna, Vienna, Austria.
  • Goeschl S; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
  • Hotzy C; Department of Neurology, Medical University of Vienna, Vienna, Austria.
  • Wagner M; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
  • Berutti R; Department of Neurology, Medical University of Vienna, Vienna, Austria.
  • Sammler E; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
  • Stögmann E; Department of Neurology, Medical University of Vienna, Vienna, Austria.
  • Zimprich A; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
Hum Genomics ; 17(1): 55, 2023 Jun 17.
Article en En | MEDLINE | ID: mdl-37330543
Early-onset dementia (EOD), with symptom onset before age 65, has a strong genetic burden. Due to genetic and clinical overlaps between different types of dementia, whole-exome sequencing (WES) has emerged as an appropriate screening method for diagnostic testing and novel gene-finding approaches. We performed WES and C9orf72 repeat testing in 60 well-defined Austrian EOD patients. Seven patients (12%) carried likely disease-causing variants in monogenic genes, PSEN1, MAPT, APP, and GRN. Five patients (8%) were APOE4 homozygote carriers. Definite and possible risk variants were detected in the genes TREM2, SORL1, ABCA7 and TBK1. In an explorative approach, we cross-checked rare gene variants in our cohort with a curated neurodegeneration candidate gene list and identified DCTN1, MAPK8IP3, LRRK2, VPS13C and BACE1 as promising candidate genes. Conclusively, 12 cases (20%) carried variants relevant to patient counseling, comparable to previously reported studies, and can thus be considered genetically resolved. Reduced penetrance, oligogenic inheritance and not yet identified high-risk genes might explain the high number of unresolved cases. To address this issue, we provide complete genetic and phenotypic information (uploaded to the European Genome-phenome Archive), enabling other researchers to cross-check variants. Thereby, we hope to increase the chance of independently finding the same gene/variant-hit in other well-defined EOD patient cohorts, thus confirming new genetic risk variants or variant combinations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Aged / Humans País/Región como asunto: Europa Idioma: En Revista: Hum Genomics Asunto de la revista: GENETICA Año: 2023 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Aged / Humans País/Región como asunto: Europa Idioma: En Revista: Hum Genomics Asunto de la revista: GENETICA Año: 2023 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido