AUTHOR=Sun Lin , Zhang Jianye , Su Ning , Zhang Shaowei , Yan Feng , Lin Xiang , Yu Jie , Li Wei , Li Xia , Xiao Shifu 

TITLE=Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.745407

DOI=10.3389/fnagi.2021.745407

ISSN=1663-4365

ABSTRACT=<p><bold>Background:</bold> Sporadic dementias generally occur in older age and are highly polygenic, which indicates some patients transmitted in a poly-genes hereditary fashion.</p><p><bold>Objective:</bold> Our study aimed to analyze the correlations of genetic features with clinical symptoms in patients with degenerative dementia.</p><p><bold>Methods:</bold> We recruited a group of 84 dementia patients and conducted the whole exome sequencing (WES). The data were analyzed focusing on 153 dementia-related causing and susceptible genes.</p><p><bold>Results:</bold> According to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, we identified four reported pathogenic variants, namely, <italic>PSEN1</italic> c.A344G, <italic>APP</italic> c.G2149A, <italic>MAPT</italic> c.G1165A, and <italic>MAPT</italic> c.G742A, one reported likely pathogenic variant, namely, <italic>PSEN2</italic> c.G100A, one novel pathogenic variants, <italic>SQSTM1</italic> c.C671A, and three novel likely pathogenic variants, namely, <italic>ABCA7</italic> c.C4690T, <italic>ATP13A2</italic> c.3135delC, and <italic>NOS3</italic> c.2897-2A &gt; G. 21 variants with uncertain significance in <italic>PSEN2</italic>, <italic>C9orf72</italic>, <italic>NOTCH3</italic>, <italic>ABCA7</italic>, <italic>ERBB4</italic>, <italic>GRN</italic>, <italic>MPO</italic>, <italic>SETX</italic>, <italic>SORL1</italic>, <italic>NEFH</italic>, <italic>ADCM10</italic>, and <italic>SORL1, etc.</italic>, were also detected in patients with Alzheimer’s disease (AD) and frontotemporal dementia (FTD).</p><p><bold>Conclusion:</bold> The new variants in dementia-related genes indicated heterogeneity in pathogenesis and phenotype of degenerative dementia. WES could serve as an efficient diagnostic tool for detecting intractable dementia.</p>