Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73678599 G>A
dbSNP ID: rs199715992
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GCT to ACT
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 10

Findings

This variant was identified in a French study that screened 129 individuals with sporadic AD diagnosed according to the National Institute of Aging–Alzheimer’s Association criteria with an age at onset below 51 (Lanoiselée et al., 2017). The mutation carrier had progressive cognitive decline beginning at age 45, and a disease duration of four years. The carrier was homozygous for the APOE3 allele. It is unknown if the mutation arose de novo, as parental DNA was unavailable. The variant was found in the exome database ExAC at a frequency of 4.118e-05.

Neuropathology
Neuropathological data are unavailable. Cerebrospinal fluid biomarkers for AD were measured in the mutation carrier, however. Although levels of Aβ42 were reduced consistent with AD (487 pg/ml), tau and phospho-tau were in the normal range (217 pg/ml; and 35 pg/ml, respectively).

Biological Effect
Unknown.
Based on the criteria developed by Guerreiro and colleagues (Guerreiro et al., 2010), this mutation was classified as possibly pathogenic (Lanoiselée et al., 2017).

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

1. Lanoiselée HM, Nicolas G, Wallon D, Rovelet-Lecrux A, Lacour M, Rousseau S, Richard AC, Pasquier F, Rollin-Sillaire A, Martinaud O, Quillard-Muraine M, de la Sayette V, Boutoleau-Bretonniere C, Etcharry-Bouyx F, Chauviré V, Sarazin M, le Ber I, Epelbaum S, Jonveaux T, Rouaud O, Ceccaldi M, Félician O, Godefroy O, Formaglio M, Croisile B, Auriacombe S, Chamard L, Vincent JL, Sauvée M, Marelli-Tosi C, Gabelle A, Ozsancak C, Pariente J, Paquet C, Hannequin D, Campion D, collaborators of the CNR-MAJ project. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med. 2017 Mar;14(3):e1002270. Epub 2017 Mar 28 PubMed.
2. Guerreiro RJ, Baquero M, Blesa R, Boada M, Brás JM, Bullido MJ, Calado A, Crook R, Ferreira C, Frank A, Gómez-Isla T, Hernández I, Lleó A, Machado A, Martínez-Lage P, Masdeu J, Molina-Porcel L, Molinuevo JL, Pastor P, Pérez-Tur J, Relvas R, Oliveira CR, Ribeiro MH, Rogaeva E, Sa A, Samaranch L, Sánchez-Valle R, Santana I, Tàrraga L, Valdivieso F, Singleton A, Hardy J, Clarimón J. 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