Mutations

PSEN1 I167del (TTAdel)

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73653579 TTA>---
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Deletion
Codon Change: TTA to ---
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 6

Findings

This deletion of three nucleotides was detected in an Alzheimer's disease patient from mainland China. The proband developed progressive memory deficits at age 38. Three years later, behavioral symptoms surfaced and she also developed spastic paraparesis. She had a positive family history; her mother died of dementia at age 55 and two older siblings were also affected (onset at ages 44 and 46). The mutation was present in the two affected siblings in addition to the proband, and therefore appears to segregate with disease in this family (Jiao et al., 2014).

Neuropathology

Unknown.

Biological Effect

In an in vitro assay with isolated proteins, an I167del mutant PSEN1 (nucleotide change unspecified) produced less Aβ42 than wild-type PSEN1, and Aβ40 production was undetectable (Sun et al., 2017). This mutation is predicted to be damaging by in silico analysis using SIFT software and definitely pathogenic according to the algorithm proposed by Guerreiro et al., 2010.

Last Updated: 22 Sep 2019

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References

Paper Citations

  1. . Mutational analysis in early-onset familial Alzheimer's disease in Mainland China. Neurobiol Aging. 2014 Aug;35(8):1957.e1-6. Epub 2014 Feb 20 PubMed.
  2. . Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485. Epub 2016 Dec 5 PubMed.
  3. . Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010 May;31(5):725-31. Epub 2008 Jul 30 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Mutational analysis in early-onset familial Alzheimer's disease in Mainland China. Neurobiol Aging. 2014 Aug;35(8):1957.e1-6. Epub 2014 Feb 20 PubMed.

Other mutations at this position

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