Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease
Amyloid protein deposition is a common mechanism of hereditary amyloidosis (HA) and Alzheimer’s disease (AD). Mutations of gelsolin (GSN), cystatin C (CST3), transthyretin (TTR), and integral membrane protein 2B (ITM2B) genes can lead to HA. But the relationship is unclear between these genes and AD...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-09-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2020.581524/full |
| _version_ | 1828844009053749248 |
|---|---|
| author | Yaling Jiang Bin Jiao Bin Jiao Bin Jiao Xinxin Liao Xinxin Liao Xinxin Liao Xuewen Xiao Xixi Liu Lu Shen Lu Shen Lu Shen Lu Shen |
| author_facet | Yaling Jiang Bin Jiao Bin Jiao Bin Jiao Xinxin Liao Xinxin Liao Xinxin Liao Xuewen Xiao Xixi Liu Lu Shen Lu Shen Lu Shen Lu Shen |
| author_sort | Yaling Jiang |
| collection | DOAJ |
| description | Amyloid protein deposition is a common mechanism of hereditary amyloidosis (HA) and Alzheimer’s disease (AD). Mutations of gelsolin (GSN), cystatin C (CST3), transthyretin (TTR), and integral membrane protein 2B (ITM2B) genes can lead to HA. But the relationship is unclear between these genes and AD. Genes targeted sequencing (GTS), including GSN, CST3, TTR, and ITM2B, 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 GSN mutations in patients with AD in the Chinese cohort. Although mutations in the GSN gene are rare, it may explain a small portion of clinically diagnosed AD. |
| first_indexed | 2024-12-12T20:56:18Z |
| format | Article |
| id | doaj.art-2f4080d8e27748f29c78a313e927e41b |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-12T20:56:18Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-2f4080d8e27748f29c78a313e927e41b2022-12-22T00:12:16ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-09-011210.3389/fnagi.2020.581524581524Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s DiseaseYaling Jiang0Bin Jiao1Bin Jiao2Bin Jiao3Xinxin Liao4Xinxin Liao5Xinxin Liao6Xuewen Xiao7Xixi Liu8Lu Shen9Lu Shen10Lu Shen11Lu Shen12Department of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Central South University, Changsha, ChinaKey Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Central South University, Changsha, ChinaKey Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Central South University, Changsha, ChinaKey Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaAmyloid protein deposition is a common mechanism of hereditary amyloidosis (HA) and Alzheimer’s disease (AD). Mutations of gelsolin (GSN), cystatin C (CST3), transthyretin (TTR), and integral membrane protein 2B (ITM2B) genes can lead to HA. But the relationship is unclear between these genes and AD. Genes targeted sequencing (GTS), including GSN, CST3, TTR, and ITM2B, 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 GSN mutations in patients with AD in the Chinese cohort. Although mutations in the GSN gene are rare, it may explain a small portion of clinically diagnosed AD.https://www.frontiersin.org/article/10.3389/fnagi.2020.581524/fullAlzheimer’s diseasehereditary amyloidosisgelsolingeneticsChina |
| spellingShingle | Yaling Jiang Bin Jiao Bin Jiao Bin Jiao Xinxin Liao Xinxin Liao Xinxin Liao Xuewen Xiao Xixi Liu Lu Shen Lu Shen Lu Shen Lu Shen Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease Frontiers in Aging Neuroscience Alzheimer’s disease hereditary amyloidosis gelsolin genetics China |
| title | Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease |
| title_full | Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease |
| title_fullStr | Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease |
| title_full_unstemmed | Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease |
| title_short | Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease |
| title_sort | analyses mutations in gsn cst3 ttr and itm2b genes in chinese patients with alzheimer s disease |
| topic | Alzheimer’s disease hereditary amyloidosis gelsolin genetics China |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2020.581524/full |
| work_keys_str_mv | AT yalingjiang analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT binjiao analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT binjiao analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT binjiao analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT xinxinliao analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT xinxinliao analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT xinxinliao analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT xuewenxiao analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT xixiliu analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT lushen analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT lushen analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT lushen analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease AT lushen analysesmutationsingsncst3ttranditm2bgenesinchinesepatientswithalzheimersdisease |