Mutations

PSEN1 V391G

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic, Parkinsonism :
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73683876 T>G
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GTT to GGT
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 11

Findings

This mutation was identified in a patient diagnosed with rapidly progressing, early AD with extrapyramidal symptoms (Lou et al., 2017). In addition to the V391G mutation, the patient carried recessive gene variants associated with extrapyramidal disease (PANK2, SYNE1, ZNF592) and had several family members who had been diagnosed with extrapyramidal disorders, including Parkinson’s disease and head tremor. The proband’s first symptoms, difficulty walking and action tremor, appeared at age 23. Within six months, motor symptoms had progressed, including the development of dysarthria and spasmodic torticollis, and impairments in short-term memory, spatial and temporal orientation, and verbal fluency developed. The unaffected parents of the patient do not carry the mutation, suggesting the mutation arose de novo.

Neuropathology
Although neuropathology data are unavailable, MRI showed generalized mild cortical and subcortical atrophy, hippocampal shrinkage, and enlarged ventricles.

Biological Effect
The mutation was predicted to be probably damaging by in silico analyses, including SIFT, Poly-Phen-2, and Mutation Taster.

Last Updated: 20 Feb 2019

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References

Paper Citations

  1. . Very early-onset sporadic Alzheimer's disease with a de novo mutation in the PSEN1 gene. Neurobiol Aging. 2017 May;53:193.e1-193.e5. Epub 2017 Jan 6 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Very early-onset sporadic Alzheimer's disease with a de novo mutation in the PSEN1 gene. Neurobiol Aging. 2017 May;53:193.e1-193.e5. Epub 2017 Jan 6 PubMed.

Other mutations at this position

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