Detection of the SQSTM1 Mutation in a Patient with Early-Onset Hippocampal Amnestic Syndrome

Article type: Short Communication

Authors: Carandini, Tiziana^{a; 1; *} | Sacchi, Luca^{a; b; 1} | Ghezzi, Laura^{b; c} | Pietroboni, Anna M.^a | Fenoglio, Chiara^{a; b} | Arighi, Andrea^a | Fumagalli, Giorgio G.^a | De Riz, Milena A.^a | Serpente, Maria^{a; b} | Rotondo, Emanuela^a | Scarpini, Elio^{a; b} | Galimberti, Daniela^{a; b}

Affiliations: [a] Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy | [b] University of Milan, Dino Ferrari Center, Milan, Italy | [c] Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

Correspondence: [*] Correspondence to: Tiziana Carandini, MD, Foundation IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy. Tel.: +39 02 5503 3845; E-mail: tizianacarandini@gmail.com.

Note: [1] These authors contributed equally to this work.

Abstract: Genetics has a major role in early-onset dementia, but the correspondence between genotype and phenotype is largely tentative. We describe a 54-year-old with familial early-onset slowly-progressive episodic memory impairment with the P392L-variant in SQSTM1. The patient showed cortical atrophy and hypometabolism in the temporal lobes, but no amyloidosis biomarkers. As symptoms/neuroimaging were suggestive for Alzheimer’s disease—but biomarkers were not—and considering the family-history, genetic analysis was performed, revealing the P392L-variant in SQSTM1, which encodes for sequestosome-1/p62. Increasing evidence suggests a p62 involvement in neurodegeneration and SQSTM1 mutations have been found to cause amyotrophic lateral sclerosis/frontotemporal dementia. Our report suggests that the clinical spectrum of SQSTM1 variants is wider.

Keywords: Alzheimer’s disease, early-onset dementia, next-generation sequencing, p62, SQSTM1

DOI: 10.3233/JAD-201231

Journal: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 477-481, 2021