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Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort

Cyclin F (CCNF) variants have been found to be associated with amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). However, the genetic and clinical characteristics of ALS patients who carry CCNF variants are largely unknown. Genetic analysis was performed for 1587 Chinese ALS patient...

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Autores principales: Zhao, Bi, Jiang, Qirui, Lin, Junyu, Wei, Qianqian, Li, Chunyu, Hou, Yanbing, Cao, Bei, Zhang, Lingyu, Ou, Ruwei, Liu, Kuncheng, Yang, Tianmi, Xiao, Yi, Huang, Rui, Shang, Huifang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224817/
https://www.ncbi.nlm.nih.gov/pubmed/37171577
http://dx.doi.org/10.1007/s12035-023-03380-1
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author Zhao, Bi
Jiang, Qirui
Lin, Junyu
Wei, Qianqian
Li, Chunyu
Hou, Yanbing
Cao, Bei
Zhang, Lingyu
Ou, Ruwei
Liu, Kuncheng
Yang, Tianmi
Xiao, Yi
Huang, Rui
Shang, Huifang
author_facet Zhao, Bi
Jiang, Qirui
Lin, Junyu
Wei, Qianqian
Li, Chunyu
Hou, Yanbing
Cao, Bei
Zhang, Lingyu
Ou, Ruwei
Liu, Kuncheng
Yang, Tianmi
Xiao, Yi
Huang, Rui
Shang, Huifang
author_sort Zhao, Bi
collection PubMed
description Cyclin F (CCNF) variants have been found to be associated with amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). However, the genetic and clinical characteristics of ALS patients who carry CCNF variants are largely unknown. Genetic analysis was performed for 1587 Chinese ALS patients, and missense variants were predicted by software analyses. Additionally, we searched PubMed, Embase, and Web of Science for relevant literature and conducted a meta-analysis of the frequency of variants. In our ALS cohort, we identified 29 nonsynonymous variants in 41 ALS patients. Among these ALS patients, 18 (1.1%) were carriers of 15 rare missense variants that were considered probably pathogenic variants, and 11 of 15 variants were novel. Seven relevant studies were identified, and a total of 43 CCNF variants in 59 ALS patients with a frequency of 0.8% were reported. The ratio of males to females in our cohort (10/8) was similar to that in Caucasian populations (4/7) and significantly higher than that in Asian populations (10/1). The proportion of bulbar onset in Caucasian CCNF carriers was similar to our cohort (25.0 vs. 27.8%); however, bulbar onset had never been reported in previous Asian studies (0/11). FTD was not found in CCNF carriers in previous Asian studies and our cohort, but it has been reported in a FALS cohort (1/75) of Caucasian individuals. There were some differences in the clinical characteristics among different ethnic ALS populations. More basic scientific studies are needed to elucidate the pathogenic mechanisms and genotype-phenotype associations of CCNF variants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03380-1.
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spelling pubmed-102248172023-05-29 Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort Zhao, Bi Jiang, Qirui Lin, Junyu Wei, Qianqian Li, Chunyu Hou, Yanbing Cao, Bei Zhang, Lingyu Ou, Ruwei Liu, Kuncheng Yang, Tianmi Xiao, Yi Huang, Rui Shang, Huifang Mol Neurobiol Article Cyclin F (CCNF) variants have been found to be associated with amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). However, the genetic and clinical characteristics of ALS patients who carry CCNF variants are largely unknown. Genetic analysis was performed for 1587 Chinese ALS patients, and missense variants were predicted by software analyses. Additionally, we searched PubMed, Embase, and Web of Science for relevant literature and conducted a meta-analysis of the frequency of variants. In our ALS cohort, we identified 29 nonsynonymous variants in 41 ALS patients. Among these ALS patients, 18 (1.1%) were carriers of 15 rare missense variants that were considered probably pathogenic variants, and 11 of 15 variants were novel. Seven relevant studies were identified, and a total of 43 CCNF variants in 59 ALS patients with a frequency of 0.8% were reported. The ratio of males to females in our cohort (10/8) was similar to that in Caucasian populations (4/7) and significantly higher than that in Asian populations (10/1). The proportion of bulbar onset in Caucasian CCNF carriers was similar to our cohort (25.0 vs. 27.8%); however, bulbar onset had never been reported in previous Asian studies (0/11). FTD was not found in CCNF carriers in previous Asian studies and our cohort, but it has been reported in a FALS cohort (1/75) of Caucasian individuals. There were some differences in the clinical characteristics among different ethnic ALS populations. More basic scientific studies are needed to elucidate the pathogenic mechanisms and genotype-phenotype associations of CCNF variants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03380-1. Springer US 2023-05-12 2023 /pmc/articles/PMC10224817/ /pubmed/37171577 http://dx.doi.org/10.1007/s12035-023-03380-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhao, Bi
Jiang, Qirui
Lin, Junyu
Wei, Qianqian
Li, Chunyu
Hou, Yanbing
Cao, Bei
Zhang, Lingyu
Ou, Ruwei
Liu, Kuncheng
Yang, Tianmi
Xiao, Yi
Huang, Rui
Shang, Huifang
Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort
title Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort
title_full Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort
title_fullStr Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort
title_full_unstemmed Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort
title_short Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort
title_sort genetic and phenotypic spectrum of amyotrophic lateral sclerosis patients with ccnf variants from a large chinese cohort
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224817/
https://www.ncbi.nlm.nih.gov/pubmed/37171577
http://dx.doi.org/10.1007/s12035-023-03380-1
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