Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr1:227076676 T>C
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CTC to CCC
Reference Isoform: PSEN2 isoform 1 (448 aa)
Genomic Region: Exon 8

Findings

This variant was identified in a German individual of European descent who developed progressive aphasia at age 54, along with memory problems (Blauwendraat et al., 2015). Speech was slow and verbal expression difficult. Behavioral symptoms developed later. The patient died at age 60. Family history was negative for neurological disease.

In a subsequent study, the variant was described as most likely having reduced penetrance, with an allele count of three, and a frequency of 0.0012 percent in the gnomAD variant database (Koriath et al., 2018).

Neuropathology

Unknown. MRI showed supratentorial cortical atrophy, particularly atrophy of the parietal cortex.

Biological Effect

Unknown. In silico, this mutation is predicted to be damaging.

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References

Paper Citations

1. Blauwendraat C, Wilke C, Jansen IE, Schulte C, Simón-Sánchez J, Metzger FG, Bender B, Gasser T, Maetzler W, Rizzu P, Heutink P, Synofzik M. Pilot whole-exome sequencing of a German early-onset Alzheimer's disease cohort reveals a substantial frequency of PSEN2 variants. Neurobiol Aging. 2016 Jan;37:208.e11-7. Epub 2015 Sep 30 PubMed.
2. Koriath C, Kenny J, Adamson G, Druyeh R, Taylor W, Beck J, Quinn L, Mok TH, Dimitriadis A, Norsworthy P, Bass N, Carter J, Walker Z, Kipps C, Coulthard E, Polke JM, Bernal-Quiros M, Denning N, Thomas R, Raybould R, Williams J, Mummery CJ, Wild EJ, Houlden H, Tabrizi SJ, Rossor MN, Hummerich H, Warren JD, Rowe JB, Rohrer JD, Schott JM, Fox NC, Collinge J, Mead S. Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series. Mol Psychiatry. 2018 Oct 2; PubMed.

Further Reading

No Available Further Reading