ArticleAlzheimer's research & therapy2018
Exome sequencing in an Italian family with Alzheimer's disease points to a role for seizure-related gene 6 (SEZ6) rare variant R615H.
Article in Alzheimer's research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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9 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Childhood-Onset Schizophrenia: A Systematic Overview of Its Genetic Heterogeneity From Classical Studies to the Genomic Era.Frontiers in genetics · 2019Pooled it
- Longitudinal protein profiling of blood during childhood into early adulthood.Nature communications · 2026Article
- SEZ6L2 Loss Disrupts Motor Coordination, Cognitive Function, and Synaptic Connectivity.bioRxiv : the preprint server for biology · 2026Article
- Seizure-Related Homolog Protein 6 (SEZ6): Biology and Therapeutic Target in Neuroendocrine Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Mutated Toll-like receptor 9 increases Alzheimer's disease risk by compromising innate immunity protection.Molecular psychiatry · 2023Article
- ADAMTS1, MPDZ, MVD, and SEZ6: candidate genes for autosomal recessive nonsyndromic hearing impairment.European journal of human genetics : EJHG · 2022Article
- Spatial RNA Sequencing Identifies Robust Markers of Vulnerable and Resistant Human Midbrain Dopamine Neurons and Their Expression in Parkinson's Disease.Frontiers in molecular neuroscience · 2021Article
- Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3.The EMBO journal · 2020Article
- Review
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8 authors at 3 institutions in 1 country.
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Abstract
backgroundThe typical familial form of Alzheimer's disease (FAD) accounts for about 5% of total Alzheimer's disease (AD) cases. Presenilins (PSEN1 and PSEN2) and amyloid-β (A4) precursor protein (APP) genes carry all reported FAD-linked mutations. However, other genetic loci may be involved in AD. For instance, seizure-related gene 6 (SEZ6) has been reported in brain development and psychiatric disorders and is differentially expressed in the cerebrospinal fluid of AD cases.
methodsWe describe a targeted exome sequencing analysis of a large Italian kindred with AD, negative for PSEN and APP variants, that indicated the SEZ6 heterozygous mutation R615H is associated with the pathology.
resultsWe overexpressed R615H mutation in H4-SW cells, finding a reduction of amyloid peptide Aβ(1-42). Sez6 expression decreased with age in a mouse model of AD (3xTG-AD), but independently from transgene expression.
conclusionsThese results support a role of exome sequencing for disease-associated variant discovery and reinforce available data on SEZ6 in AD models.
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