Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73653590 --->TAT
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Insertion/Deletion
Codon Change: --- to TAT
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 6

Findings

This in-frame insertion of a tyrosine between serine 170 and leucine 171 was found in a U.K. genetic screen of more than 3,000 samples of patients with dementia (Koriath et al., 2018). The mutation carrier was a woman diagnosed with AD, with unknown family history of the disease. Her symptoms emerged at age 38. The mutation was absent from genetic variant databases, including ExAC and gnomAD.

Neuropathology
Unknown

Biological Effect
The biological effect of this mutation is unknown. The site is within PSEN1 transmembrane domain 3, and pathogenic mutations in adjacent amino acids on both sides have been reported. Based on their proposed pathogenicity algorithm, Koriath and colleagues classified the mutation as likely deleterious.

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References

Paper Citations

1. 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