J Mov Disord.  2018 Jan;11(1):45-48. 10.14802/jmd.17066.

PSEN1 p.Met233Val in a Complex Neurodegenerative Movement and Neuropsychiatric Disorder

• Appel-Cresswell S
• Guella I
• Lehman A
• Foti D
• Farrer MJ

• KMID: 2405202
• DOI: http://doi.org/10.14802/jmd.17066

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.

Keyword

Neurodegeneration; exome; bioinformatics; Alzheimer; mutation

MeSH Terms

Alzheimer Disease
Ataxia
Computational Biology
Dystonia
Exome
Hallucinations
Humans
Muscle Spasticity
Myoclonus
Nervous System Diseases
Parkinsonian Disorders
Presenilin-1
Seizures
Statistics as Topic
Tremor
Presenilin-1