The role of genetics in neurodegenerative dementia: a large cohort study in South China
Abstract Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and complicated etiology. There exist potential genetic component overlaps between different neurodegenerative dementias. Here, 1795 patients with neurodegenerative dementias from South China were enroll...
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2021
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oai:doaj.org-article:781a0389d6524b80b0bbd997eb7529dc2021-12-02T18:50:45ZThe role of genetics in neurodegenerative dementia: a large cohort study in South China10.1038/s41525-021-00235-32056-7944https://doaj.org/article/781a0389d6524b80b0bbd997eb7529dc2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00235-3https://doaj.org/toc/2056-7944Abstract Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and complicated etiology. There exist potential genetic component overlaps between different neurodegenerative dementias. Here, 1795 patients with neurodegenerative dementias from South China were enrolled, including 1592 with Alzheimer’s disease (AD), 110 with frontotemporal dementia (FTD), and 93 with dementia with Lewy bodies (DLB). Genes targeted sequencing analysis were performed. According to the American College of Medical Genetics (ACMG) guidelines, 39 pathogenic/likely pathogenic (P/LP) variants were identified in 47 unrelated patients in 14 different genes, including PSEN1, PSEN2, APP, MAPT, GRN, CHCHD10, TBK1, VCP, HTRA1, OPTN, SQSTM1, SIGMAR1, and abnormal repeat expansions in C9orf72 and HTT. Overall, 33.3% (13/39) of the variants were novel, the identified P/LP variants were seen in 2.2% (35/1592) and 10.9% (12/110) of AD and FTD cases, respectively. The overall molecular diagnostic rate was 2.6%. Among them, PSEN1 was the most frequently mutated gene (46.8%, 22/47), followed by PSEN2 and APP. Additionally, the age at onset of patients with P/LP variants (51.4 years), ranging from 30 to 83 years, was ~10 years earlier than those without P/LP variants (p < 0.05). This study sheds insight into the genetic spectrum and clinical manifestations of neurodegenerative dementias in South China, further expands the existing repertoire of P/LP variants involved in known dementia-associated genes. It provides a new perspective for basic research on genetic pathogenesis and novel guiding for clinical practice of neurodegenerative dementia.Bin JiaoHui LiuLina GuoXuewen XiaoXinxin LiaoYafang ZhouLing WengLu ZhouXin WangYaling JiangQijie YangYuan ZhuLin ZhouWeiwei ZhangJunling WangXinxiang YanJinchen LiBeisha TangLu ShenNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-10 (2021) |
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DOAJ |
| collection |
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Medicine R Genetics QH426-470 |
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Medicine R Genetics QH426-470 Bin Jiao Hui Liu Lina Guo Xuewen Xiao Xinxin Liao Yafang Zhou Ling Weng Lu Zhou Xin Wang Yaling Jiang Qijie Yang Yuan Zhu Lin Zhou Weiwei Zhang Junling Wang Xinxiang Yan Jinchen Li Beisha Tang Lu Shen The role of genetics in neurodegenerative dementia: a large cohort study in South China |
| description |
Abstract Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and complicated etiology. There exist potential genetic component overlaps between different neurodegenerative dementias. Here, 1795 patients with neurodegenerative dementias from South China were enrolled, including 1592 with Alzheimer’s disease (AD), 110 with frontotemporal dementia (FTD), and 93 with dementia with Lewy bodies (DLB). Genes targeted sequencing analysis were performed. According to the American College of Medical Genetics (ACMG) guidelines, 39 pathogenic/likely pathogenic (P/LP) variants were identified in 47 unrelated patients in 14 different genes, including PSEN1, PSEN2, APP, MAPT, GRN, CHCHD10, TBK1, VCP, HTRA1, OPTN, SQSTM1, SIGMAR1, and abnormal repeat expansions in C9orf72 and HTT. Overall, 33.3% (13/39) of the variants were novel, the identified P/LP variants were seen in 2.2% (35/1592) and 10.9% (12/110) of AD and FTD cases, respectively. The overall molecular diagnostic rate was 2.6%. Among them, PSEN1 was the most frequently mutated gene (46.8%, 22/47), followed by PSEN2 and APP. Additionally, the age at onset of patients with P/LP variants (51.4 years), ranging from 30 to 83 years, was ~10 years earlier than those without P/LP variants (p < 0.05). This study sheds insight into the genetic spectrum and clinical manifestations of neurodegenerative dementias in South China, further expands the existing repertoire of P/LP variants involved in known dementia-associated genes. It provides a new perspective for basic research on genetic pathogenesis and novel guiding for clinical practice of neurodegenerative dementia. |
| format |
article |
| author |
Bin Jiao Hui Liu Lina Guo Xuewen Xiao Xinxin Liao Yafang Zhou Ling Weng Lu Zhou Xin Wang Yaling Jiang Qijie Yang Yuan Zhu Lin Zhou Weiwei Zhang Junling Wang Xinxiang Yan Jinchen Li Beisha Tang Lu Shen |
| author_facet |
Bin Jiao Hui Liu Lina Guo Xuewen Xiao Xinxin Liao Yafang Zhou Ling Weng Lu Zhou Xin Wang Yaling Jiang Qijie Yang Yuan Zhu Lin Zhou Weiwei Zhang Junling Wang Xinxiang Yan Jinchen Li Beisha Tang Lu Shen |
| author_sort |
Bin Jiao |
| title |
The role of genetics in neurodegenerative dementia: a large cohort study in South China |
| title_short |
The role of genetics in neurodegenerative dementia: a large cohort study in South China |
| title_full |
The role of genetics in neurodegenerative dementia: a large cohort study in South China |
| title_fullStr |
The role of genetics in neurodegenerative dementia: a large cohort study in South China |
| title_full_unstemmed |
The role of genetics in neurodegenerative dementia: a large cohort study in South China |
| title_sort |
role of genetics in neurodegenerative dementia: a large cohort study in south china |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/781a0389d6524b80b0bbd997eb7529dc |
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