Frontiers in Aging Neuroscience (Feb 2023)
Genetic and clinical analysis of TP73 gene in amyotrophic lateral sclerosis patients from Chinese mainland
- Xuxiong Tang,
- Yanchun Yuan,
- Zhen Liu,
- Yue Bu,
- Linxin Tang,
- Qianqian Zhao,
- Bin Jiao,
- Bin Jiao,
- Bin Jiao,
- Bin Jiao,
- Bin Jiao,
- Jifeng Guo,
- Jifeng Guo,
- Jifeng Guo,
- Jifeng Guo,
- Jifeng Guo,
- Lu Shen,
- Lu Shen,
- Lu Shen,
- Lu Shen,
- Lu Shen,
- Hong Jiang,
- Hong Jiang,
- Hong Jiang,
- Hong Jiang,
- Hong Jiang,
- Beisha Tang,
- Beisha Tang,
- Beisha Tang,
- Beisha Tang,
- Beisha Tang,
- Junling Wang,
- Junling Wang,
- Junling Wang,
- Junling Wang,
- Junling Wang
Affiliations
- Xuxiong Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Yanchun Yuan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Zhen Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Yue Bu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Linxin Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Qianqian Zhao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Bin Jiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Bin Jiao
- National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Bin Jiao
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China
- Bin Jiao
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Bin Jiao
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
- Jifeng Guo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Jifeng Guo
- National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Jifeng Guo
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China
- Jifeng Guo
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Jifeng Guo
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
- Lu Shen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Lu Shen
- National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Lu Shen
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China
- Lu Shen
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Lu Shen
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
- Hong Jiang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hong Jiang
- National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hong Jiang
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China
- Hong Jiang
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Hong Jiang
- School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Beisha Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Beisha Tang
- National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Beisha Tang
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China
- Beisha Tang
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Beisha Tang
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
- Junling Wang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Junling Wang
- National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Junling Wang
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China
- Junling Wang
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Junling Wang
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
- DOI
- https://doi.org/10.3389/fnagi.2023.1114022
- Journal volume & issue
-
Vol. 15
Abstract
IntroductionTP73 was recently identified as a novel causative gene for amyotrophic lateral sclerosis (ALS). We aimed to determine the contribution of variations in TP73 in the Chinese ALS population and to further explore the genotype-phenotype correlations.MethodsWe screened rare, putative pathogenic TP73 mutations in a large Chinese ALS cohort and performed association analysis of both rare and common TP73 variations between cases and controls.ResultsOf the 985 ALS patients studied, six rare, heterozygous putative pathogenic variants in TP73 were identified among six unrelated sALS patients. Exon 14 of TP73 might be a mutant hotspot in our cohort. Patients with ALS with only rare, putative pathogenic TP73 mutations exhibited a characteristic clinical profile. Patients harboring multiple mutations in TP73 and other ALS-related genes displayed a significantly earlier onset of ALS. Association analysis revealed that rare TP73 variants in the untranslated regions (UTRs) were enriched among ALS patients; meanwhile, two common variants in the exon-intron boundary were discovered to be associated with ALS.DiscussionWe demonstrate that TP73 variations also have contributed to ALS in the Asian population and broaden the genotypic and phenotypic spectrum of TP73 variants in the ALS-frontotemporal dementia (FTD) spectrum. Furthermore, our findings first suggest that TP73 is not only a causative gene, but also exerts a disease-modifying effect. These results may contribute to a better understanding of the molecular mechanism of ALS.
Keywords
- amyotrophic lateral sclerosis
- TP73
- gene mutation
- phenotype–genotype association
- neurodegenerative disease
- clinical characteristic