Overview

Clinical Phenotype: Alzheimer's Disease
Position: (GRCh38/hg38):Chr11:121586320 C>T
Position: (GRCh37/hg19):Chr11:121457029 C>T
dbSNP ID: NA
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected Protein Consequence: Nonsense
Codon Change: CAG to TAG
Reference Isoform: SORL1 Isoform 1 (2214 aa)
Genomic Region: Exon 27

Findings

This protein-truncating variant was identified in an Alzheimer’s case from the Centre National de Référence - Malades Alzheimer Jeunes (CNR-MAJ), the French national reference center for young Alzheimer patients (Bellenguez et al., 2017, 28789839; Schramm et al., 2022, 35761418). This carrier was 51 years old at symptom onset, with an APOE genotype of APOE E3/E4. There was a family history of AD, with multiple affected individuals seen in a three-generation pedigree. In addition to the proband, genotype information is available from four family members: the affected parent of the proband (age of onset 73 years, APOE E3/E4) and an unaffected cousin (cognitively intact at 68, APOE E2/E4) carry the variant, while an unaffected cousin (cognitively intact at 42, APOE E3/E3) and unaffected aunt or uncle (cognitively intact at 86, APOE E3/E3) do not.

In a study that included 15,808 Alzheimer’s cases and 16,097 control subjects from multiple European and American cohorts, including CNR-MAJ, this allele was observed once among the AD cases (Holstege et al., 2022).

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

1. Holstege H, Hulsman M, Charbonnier C, Grenier-Boley B, Quenez O, Grozeva D, van Rooij JG, Sims R, Ahmad S, Amin N, Norsworthy PJ, Dols-Icardo O, Hummerich H, Kawalia A, Amouyel P, Beecham GW, Berr C, Bis JC, Boland A, Bossù P, Bouwman F, Bras J, Campion D, Cochran JN, Daniele A, Dartigues JF, Debette S, Deleuze JF, Denning N, DeStefano AL, Farrer LA, Fernández MV, Fox NC, Galimberti D, Genin E, Gille JJ, Le Guen Y, Guerreiro R, Haines JL, Holmes C, Ikram MA, Ikram MK, Jansen IE, Kraaij R, Lathrop M, Lemstra AW, Lleó A, Luckcuck L, Mannens MM, Marshall R, Martin ER, Masullo C, Mayeux R, Mecocci P, Meggy A, Mol MO, Morgan K, Myers RM, Nacmias B, Naj AC, Napolioni V, Pasquier F, Pastor P, Pericak-Vance MA, Raybould R, Redon R, Reinders MJ, Richard AC, Riedel-Heller SG, Rivadeneira F, Rousseau S, Ryan NS, Saad S, Sanchez-Juan P, Schellenberg GD, Scheltens P, Schott JM, Seripa D, Seshadri S, Sie D, Sistermans EA, Sorbi S, van Spaendonk R, Spalletta G, Tesi N, Tijms B, Uitterlinden AG, van der Lee SJ, Visser PJ, Wagner M, Wallon D, Wang LS, Zarea A, Clarimon J, van Swieten JC, Greicius MD, Yokoyama JS, Cruchaga C, Hardy J, Ramirez A, Mead S, van der Flier WM, van Duijn CM, Williams J, Nicolas G, Bellenguez C, Lambert JC. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease. Nat Genet. 2022 Dec;54(12):1786-1794. Epub 2022 Nov 21 PubMed.

Further Reading

No Available Further Reading