Mutations

PSEN2 N141Y

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1):
Genomic Mutation Name (NT1):
dbSNP ID: rs61761208
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: AAC to TAC

Findings

This mutation was identified in a Chinese Han family from northern China. It is thought to be the first pathogenic PSEN2 mutation described in a Chinese family. The reported pedigree shows six affected members over three generations. The proband noticed forgetfulness at age 43 and died at age 55 with autopsy-confirmed Alzheimer's disease. Her grandfather, mother, and two aunts were also affected and died of dementia in their sixth decade. The proband's two brothers, who were developmentally delayed, died of cerebral hemorrhage in their forties, reportedly without dementia. Segregation analysis supported pathogenicity; the N141Y mutation was detected in two affected family members and absent in five unaffected family members. It was also absent in 188 unrelated individuals (Niu et al., 2014).

Neuropathology

The proband had autopsy-confirmed AD with severe brain atrophy, especially of the parietal lobe, and numerous plaques and neurofibrillary tangles.

Biological Effect

Unknown. In silico analysis using SIFT, PolyPhen-2, and other programs, predicted a damaging and/or probably damaging effect.

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References

Paper Citations

  1. . A novel mutation in the PSEN2 gene (N141Y) associated with early-onset autosomal dominant Alzheimer's disease in a Chinese Han family. Neurobiol Aging. 2014 Oct;35(10):2420.e1-5. Epub 2014 Apr 18 PubMed.

Further Reading

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Primary Papers

  1. . A novel mutation in the PSEN2 gene (N141Y) associated with early-onset autosomal dominant Alzheimer's disease in a Chinese Han family. Neurobiol Aging. 2014 Oct;35(10):2420.e1-5. Epub 2014 Apr 18 PubMed.

Other mutations at this position

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