Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
Publ. Version/Full Text
DOI
PMC
 |
Open Access Gold |
|
as soon as is submitted to ZB.
Comprehensive genetic screening of early-onset dementia patients in an Austrian cohort-suggesting new disease-contributing genes.
Hum. Genomics 17:55 (2023)
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.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Early-onset Dementia ; Genetic Variants ; Whole-exome Sequencing; Alzheimers-disease; Diagnostic-criteria; Cerebrospinal-fluid; Lrrk2 Kinase; Mutations; Phenotype; Variant; Heterogeneity; Transport
ISSN (print) / ISBN
1473-9542
e-ISSN
1479-7364
Journal
Human genomics
Quellenangaben
Volume: 17,
Issue: 1,
Article Number: 55
Publisher
Stewart
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Neurogenomics (ING)