Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing
Background: Sporadic dementias generally occur in older age and are highly polygenic, which indicates some patients transmitted in a poly-genes hereditary fashion.Objective: Our study aimed to analyze the correlations of genetic features with clinical symptoms in patients with degenerative dementia....
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-10-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.745407/full |
| _version_ | 1818738419846610944 |
|---|---|
| author | Lin Sun Jianye Zhang Ning Su Shaowei Zhang Feng Yan Xiang Lin Jie Yu Wei Li Xia Li Shifu Xiao |
| author_facet | Lin Sun Jianye Zhang Ning Su Shaowei Zhang Feng Yan Xiang Lin Jie Yu Wei Li Xia Li Shifu Xiao |
| author_sort | Lin Sun |
| collection | DOAJ |
| description | Background: Sporadic dementias generally occur in older age and are highly polygenic, which indicates some patients transmitted in a poly-genes hereditary fashion.Objective: Our study aimed to analyze the correlations of genetic features with clinical symptoms in patients with degenerative dementia.Methods: 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.Results: According to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, we identified four reported pathogenic variants, namely, PSEN1 c.A344G, APP c.G2149A, MAPT c.G1165A, and MAPT c.G742A, one reported likely pathogenic variant, namely, PSEN2 c.G100A, one novel pathogenic variants, SQSTM1 c.C671A, and three novel likely pathogenic variants, namely, ABCA7 c.C4690T, ATP13A2 c.3135delC, and NOS3 c.2897-2A > G. 21 variants with uncertain significance in PSEN2, C9orf72, NOTCH3, ABCA7, ERBB4, GRN, MPO, SETX, SORL1, NEFH, ADCM10, and SORL1, etc., were also detected in patients with Alzheimer’s disease (AD) and frontotemporal dementia (FTD).Conclusion: 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. |
| first_indexed | 2024-12-18T01:08:39Z |
| format | Article |
| id | doaj.art-27b4857978bc423d936b3dd18b961272 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-18T01:08:39Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-27b4857978bc423d936b3dd18b9612722022-12-21T21:26:09ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-10-011310.3389/fnagi.2021.745407745407Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome SequencingLin SunJianye ZhangNing SuShaowei ZhangFeng YanXiang LinJie YuWei LiXia LiShifu XiaoBackground: Sporadic dementias generally occur in older age and are highly polygenic, which indicates some patients transmitted in a poly-genes hereditary fashion.Objective: Our study aimed to analyze the correlations of genetic features with clinical symptoms in patients with degenerative dementia.Methods: 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.Results: According to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, we identified four reported pathogenic variants, namely, PSEN1 c.A344G, APP c.G2149A, MAPT c.G1165A, and MAPT c.G742A, one reported likely pathogenic variant, namely, PSEN2 c.G100A, one novel pathogenic variants, SQSTM1 c.C671A, and three novel likely pathogenic variants, namely, ABCA7 c.C4690T, ATP13A2 c.3135delC, and NOS3 c.2897-2A > G. 21 variants with uncertain significance in PSEN2, C9orf72, NOTCH3, ABCA7, ERBB4, GRN, MPO, SETX, SORL1, NEFH, ADCM10, and SORL1, etc., were also detected in patients with Alzheimer’s disease (AD) and frontotemporal dementia (FTD).Conclusion: 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.https://www.frontiersin.org/articles/10.3389/fnagi.2021.745407/fullAlzheimer’s diseasefrontotemporal lobe degenerationdementianext-generation sequencingwhole exome sequencing (WES) |
| spellingShingle | Lin Sun Jianye Zhang Ning Su Shaowei Zhang Feng Yan Xiang Lin Jie Yu Wei Li Xia Li Shifu Xiao Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing Frontiers in Aging Neuroscience Alzheimer’s disease frontotemporal lobe degeneration dementia next-generation sequencing whole exome sequencing (WES) |
| title | Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing |
| title_full | Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing |
| title_fullStr | Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing |
| title_full_unstemmed | Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing |
| title_short | Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing |
| title_sort | analysis of genotype phenotype correlations in patients with degenerative dementia through the whole exome sequencing |
| topic | Alzheimer’s disease frontotemporal lobe degeneration dementia next-generation sequencing whole exome sequencing (WES) |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.745407/full |
| work_keys_str_mv | AT linsun analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT jianyezhang analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT ningsu analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT shaoweizhang analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT fengyan analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT xianglin analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT jieyu analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT weili analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT xiali analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing AT shifuxiao analysisofgenotypephenotypecorrelationsinpatientswithdegenerativedementiathroughthewholeexomesequencing |