AUTHOR=Jiang Yaling , Jiao Bin , Liao Xinxin , Xiao Xuewen , Liu Xixi , Shen Lu 

TITLE=Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=12

YEAR=2020

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.581524

DOI=10.3389/fnagi.2020.581524

ISSN=1663-4365

ABSTRACT=<p>Amyloid protein deposition is a common mechanism of hereditary amyloidosis (HA) and Alzheimer’s disease (AD). Mutations of g<italic>elsolin</italic> (<italic>GSN</italic>), <italic>cystatin C</italic> (<italic>CST3</italic>), <italic>transthyretin</italic> (<italic>TTR</italic>), and <italic>integral membrane protein 2B</italic> (<italic>ITM2B</italic>) genes can lead to HA. But the relationship is unclear between these genes and AD. Genes targeted sequencing (GTS), including <italic>GSN, CST3, TTR</italic>, and <italic>ITM2B</italic>, was performed in a total of 636 patients with clinical AD and 365 normal controls from China. As a result, according to American College of Medical Genetics and Genomics (ACMG) guidelines, two novel likely pathogenic frame-shift mutations (GSN:c.1036delA:p.K346fs and GSN:c.8_35del:p.P3fs) were detected in five patients with AD, whose initial symptom was memory decline, accompanied with psychological and behavioral abnormalities later. Interestingly, the patient with K346fs mutation, presented cerebral β-amyloid protein deposition, had an early onset (48 years) and experienced rapid progression, while the other four patients with P3fs mutation had a late onset [(Mean ± SD): 69.50 ± 5.20 years] and a long course of illness [(Mean ± SD): 9.24 ± 4.86 years]. Besides, we also discovered 17 variants of uncertain significance (VUS) in these four genes. To our knowledge, we are the first to report AD phenotype with <italic>GSN</italic> mutations in patients with AD in the Chinese cohort. Although mutations in the <italic>GSN</italic> gene are rare, it may explain a small portion of clinically diagnosed AD.</p>