Abstract
Molecular genetic research provides unprecedented opportunities to examine genotype-phenotype correlations underlying complex syndromes. To investigate pathogenic mutations and genotype-phenotype relationships in diverse neurodegenerative conditions, we performed a rare variant analysis of damaging mutations in autopsy-confirmed neurodegenerative cases from the Johns Hopkins Brain Resource Center (n = 1243 patients). We used NeuroChip genotyping and C9orf72 hexanucleotide repeat analysis to rapidly screen our cohort for disease-causing mutations. In total, we identified 42 individuals who carried a pathogenic mutation in LRRK2, GBA, APP, PSEN1, MAPT, GRN, C9orf72, SETX, SPAST, or CSF1R, and we provide a comprehensive description of the diverse clinicopathological features of these well-characterized cases. Our study highlights the utility of high-throughput genetic screening arrays to establish a molecular diagnosis in individuals with complex neurodegenerative syndromes, to broaden disease phenotypes and to provide insights into unexpected disease associations.
Original language | English (US) |
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Pages (from-to) | 214.e1-214.e9 |
Journal | Neurobiology of aging |
Volume | 76 |
DOIs | |
State | Published - Apr 2019 |
Keywords
- Brain bank
- Genotype-phenotype
- NeuroChip
- Neurodegeneration
ASJC Scopus subject areas
- Clinical Neurology
- Geriatrics and Gerontology
- Aging
- General Neuroscience
- Developmental Biology