Clinical genome sequencing in neurodegenerative diseases-outcome in the first 500 patients.
Genome sequencing diagnosed 12% of neurodegenerative disease patients tested.
Clinical genome sequencing in neurodegenerative diseases-outcome in the first 500 patients.
Neurodegenerative diseases (neurodegenerative diseases) are clinically and genetically heterogeneous, requiring neuropathology or molecular testing for a definitive diagnosis.
This study assesses the diagnostic performance of whole genome sequencing in individuals with neurodegenerative diseases.
By allowing simultaneous detection of single-nucleotide variants, copy-number variants, structural variants, and repeat expansions, whole genome sequencing has the potential to improve diagnostic yield, facilitate genetic counseling and support clinical trial inclusion.
genome sequencing pinpointed the cause in about 1 in 8 patients
These variants were found in 16 different genes, with C9orf72 being the most prevalent.
Repeat expansions represented the largest variant class, accounting for 35 of 61 LP/P cases (57%); most of which were C9orf72 expansions (31/35).
In the largest phenotype groups, frontotemporal dementia (frontotemporal dementia) had the highest diagnostic yield (19%) followed by amyotrophic lateral sclerosis (ALS, 13%), whereas an underlying monogenic cause was expectedly low in Alzheimer disease (AD, 4%).
In frontotemporal dementia and ALS, these results support universal access to genetic testing independent of age at onset or family history.