Cargando…
Novel FGFR1 Variants Are Associated with Congenital Scoliosis
FGFR1 encodes a transmembrane cytokine receptor, which is involved in the early development of the human embryo and plays an important role in gastrulation, organ specification and patterning of various tissues. Pathogenic FGFR1 variants have been associated with Kallmann syndrome and hypogonadotrop...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393897/ https://www.ncbi.nlm.nih.gov/pubmed/34440300 http://dx.doi.org/10.3390/genes12081126 |
_version_ | 1783743828624146432 |
---|---|
author | Wang, Shengru Chai, Xiran Yan, Zihui Zhao, Sen Yang, Yang Li, Xiaoxin Niu, Yuchen Lin, Guanfeng Su, Zhe Wu, Zhihong Zhang, Terry Jianguo Wu, Nan |
author_facet | Wang, Shengru Chai, Xiran Yan, Zihui Zhao, Sen Yang, Yang Li, Xiaoxin Niu, Yuchen Lin, Guanfeng Su, Zhe Wu, Zhihong Zhang, Terry Jianguo Wu, Nan |
author_sort | Wang, Shengru |
collection | PubMed |
description | FGFR1 encodes a transmembrane cytokine receptor, which is involved in the early development of the human embryo and plays an important role in gastrulation, organ specification and patterning of various tissues. Pathogenic FGFR1 variants have been associated with Kallmann syndrome and hypogonadotropic hypogonadism. In our congenital scoliosis (CS) patient series of 424 sporadic CS patients under the framework of the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study, we identified four unrelated patients harboring FGFR1 variants, including one frameshift and three missense variants. These variants were predicted to be deleterious by in silico prediction and conservation analysis. Signaling activities and expression levels of the mutated protein were evaluated in vitro and compared to that of the wild type (WT) FGFR1. As a result, the overall protein expressions of c.2334dupC, c.2339T>C and c.1261A>G were reduced to 43.9%, 63.4% and 77.4%, respectively. By the reporter gene assay, we observed significantly reduced activity for c.2334dupC, c.2339T>C and c.1261A>G, indicating the diminished FGFR1 signaling pathway. In conclusion, FGFR1 variants identified in our patients led to only mild disruption to protein function, caused milder skeletal and cardiac phenotypes than those reported previously. |
format | Online Article Text |
id | pubmed-8393897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83938972021-08-28 Novel FGFR1 Variants Are Associated with Congenital Scoliosis Wang, Shengru Chai, Xiran Yan, Zihui Zhao, Sen Yang, Yang Li, Xiaoxin Niu, Yuchen Lin, Guanfeng Su, Zhe Wu, Zhihong Zhang, Terry Jianguo Wu, Nan Genes (Basel) Article FGFR1 encodes a transmembrane cytokine receptor, which is involved in the early development of the human embryo and plays an important role in gastrulation, organ specification and patterning of various tissues. Pathogenic FGFR1 variants have been associated with Kallmann syndrome and hypogonadotropic hypogonadism. In our congenital scoliosis (CS) patient series of 424 sporadic CS patients under the framework of the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study, we identified four unrelated patients harboring FGFR1 variants, including one frameshift and three missense variants. These variants were predicted to be deleterious by in silico prediction and conservation analysis. Signaling activities and expression levels of the mutated protein were evaluated in vitro and compared to that of the wild type (WT) FGFR1. As a result, the overall protein expressions of c.2334dupC, c.2339T>C and c.1261A>G were reduced to 43.9%, 63.4% and 77.4%, respectively. By the reporter gene assay, we observed significantly reduced activity for c.2334dupC, c.2339T>C and c.1261A>G, indicating the diminished FGFR1 signaling pathway. In conclusion, FGFR1 variants identified in our patients led to only mild disruption to protein function, caused milder skeletal and cardiac phenotypes than those reported previously. MDPI 2021-07-24 /pmc/articles/PMC8393897/ /pubmed/34440300 http://dx.doi.org/10.3390/genes12081126 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Shengru Chai, Xiran Yan, Zihui Zhao, Sen Yang, Yang Li, Xiaoxin Niu, Yuchen Lin, Guanfeng Su, Zhe Wu, Zhihong Zhang, Terry Jianguo Wu, Nan Novel FGFR1 Variants Are Associated with Congenital Scoliosis |
title | Novel FGFR1 Variants Are Associated with Congenital Scoliosis |
title_full | Novel FGFR1 Variants Are Associated with Congenital Scoliosis |
title_fullStr | Novel FGFR1 Variants Are Associated with Congenital Scoliosis |
title_full_unstemmed | Novel FGFR1 Variants Are Associated with Congenital Scoliosis |
title_short | Novel FGFR1 Variants Are Associated with Congenital Scoliosis |
title_sort | novel fgfr1 variants are associated with congenital scoliosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393897/ https://www.ncbi.nlm.nih.gov/pubmed/34440300 http://dx.doi.org/10.3390/genes12081126 |
work_keys_str_mv | AT wangshengru novelfgfr1variantsareassociatedwithcongenitalscoliosis AT chaixiran novelfgfr1variantsareassociatedwithcongenitalscoliosis AT yanzihui novelfgfr1variantsareassociatedwithcongenitalscoliosis AT zhaosen novelfgfr1variantsareassociatedwithcongenitalscoliosis AT yangyang novelfgfr1variantsareassociatedwithcongenitalscoliosis AT lixiaoxin novelfgfr1variantsareassociatedwithcongenitalscoliosis AT niuyuchen novelfgfr1variantsareassociatedwithcongenitalscoliosis AT linguanfeng novelfgfr1variantsareassociatedwithcongenitalscoliosis AT suzhe novelfgfr1variantsareassociatedwithcongenitalscoliosis AT wuzhihong novelfgfr1variantsareassociatedwithcongenitalscoliosis AT zhangterryjianguo novelfgfr1variantsareassociatedwithcongenitalscoliosis AT wunan novelfgfr1variantsareassociatedwithcongenitalscoliosis |