PSEN1 p.Met233Val in a Complex Neurodegenerative Movement and Neuropsychiatric Disorder
- Author:
Silke APPEL-CRESSWELL
1
;
Ilaria GUELLA
;
Anna LEHMAN
;
Dean FOTI
;
Matthew J FARRER
Author Information
- Publication Type:Case Report
- Keywords: Neurodegeneration; exome; bioinformatics; Alzheimer; mutation
- MeSH: Alzheimer Disease; Ataxia; Computational Biology; Dystonia; Exome; Hallucinations; Humans; Muscle Spasticity; Myoclonus; Nervous System Diseases; Parkinsonian Disorders; Presenilin-1; Seizures; Statistics as Topic; Tremor
- From:Journal of Movement Disorders 2018;11(1):45-48
- CountryRepublic of Korea
- Language:English
- Abstract: Mutations in presenilin 1 (PSEN1) are the most common cause of autosomal dominant Alzheimer's disease. Here, we report a Canadian-Vietnamese family carrying a PSEN1 p.Met233Val mutation with an exceptionally early and severe presentation that includes a wide range of atypical symptoms, including prominent ataxia, Parkinsonism, spasticity, dystonia, action tremor, myoclonus, bulbar symptoms, seizures, hallucinations and behavioral changes. Whole-exome sequencing (WES) was performed on the affected proband after many assessments over several years proved diagnostically inconclusive. The results were analyzed using the AnnEx “Annotated Exomes” browser (http://annex.can.ubc.ca), a web-based platform that facilitates WES variant annotation and interpretation. High-throughput sequencing can be especially informative for complex neurological disorders, and WES warrants consideration as a first-line clinical test. Data analyses facilitated by web-based bioinformatics tools have great potential for novel insight, although confirmatory, diagnostically accredited Sanger sequencing is recommended prior to reporting.
