Identification of a Rare PSEN1 Mutation (Thr119Ile) in Late-Onset Alzheimer's Disease With Early Presentation of Behavioral Disturbance

Shouzi Zhang; Xiang Li; Li Zhang; Xiangyan Meng; Li Ma; Guangze Zhang; Haiyan Wu; Ling Liang; Meng Cao; Fan Mei

doi:10.3389/fpsyt.2020.00347

Identification of a Rare PSEN1 Mutation (Thr119Ile) in Late-Onset Alzheimer's Disease With Early Presentation of Behavioral Disturbance

Front Psychiatry. 2020 May 14:11:347. doi: 10.3389/fpsyt.2020.00347. eCollection 2020.

Authors

Shouzi Zhang¹, Xiang Li², Li Zhang¹, Xiangyan Meng², Li Ma¹, Guangze Zhang², Haiyan Wu¹, Ling Liang², Meng Cao¹, Fan Mei²

Affiliations

¹ Psychiatry Department, Beijing Geriatric Hospital, Beijing, China.
² Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

Abstract

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. In this study, whole genome sequencing identifies one rare and likely pathogenic mutation in the presenilin 1 (PSEN1) gene (c.356C > T, p.T119I) associated with a frontal variant of AD. Affected individuals in the kindred developed late-onset cognitive decline accompanied with early presentation of psychiatric symptoms. Positive amyloid PiB PET tracing suggested presence of pathophysiological biomarker for AD. Whole genome sequencing analysis evaluated rare coding mutations in susceptible genes for various types of dementia and supported the role of PSEN1 as a causal gene. Identification of this T119I variant in PSEN1 might broaden the spectrum of genetic basis and clinical diversity of familial AD.

Keywords: Alzheimer’s disease; PSEN1 mutation; behavioral disturbance; rare coding variants; whole genome sequencing.