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The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis
Depletion of ptk7 is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of PTK7 has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of PTK7 in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619039/ https://www.ncbi.nlm.nih.gov/pubmed/34828397 http://dx.doi.org/10.3390/genes12111791 |
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author | Su, Zhe Yang, Yang Wang, Shengru Zhao, Sen Zhao, Hengqiang Li, Xiaoxin Niu, Yuchen Qiu, Guixing Wu, Zhihong Wu, Nan Zhang, Terry Jianguo |
author_facet | Su, Zhe Yang, Yang Wang, Shengru Zhao, Sen Zhao, Hengqiang Li, Xiaoxin Niu, Yuchen Qiu, Guixing Wu, Zhihong Wu, Nan Zhang, Terry Jianguo |
author_sort | Su, Zhe |
collection | PubMed |
description | Depletion of ptk7 is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of PTK7 has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of PTK7 in 583 patients with CS and 302 patients with AIS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study. We identified a total of four rare variants in CS and four variants in AIS, including one protein truncating variant (c.464_465delAC) in a patient with CS. We then explored the effects of these variants on protein expression and sub-cellular location. We confirmed that the c.464_465delAC variant causes loss-of-function (LoF) of PTK7. In addition, the c.353C>T and c.2290G>A variants identified in two patients with AIS led to reduced protein expression of PTK7 as compared to that of the wild type. In conclusion, LoF and hypomorphic variants are associated with CS and AIS, respectively. |
format | Online Article Text |
id | pubmed-8619039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86190392021-11-27 The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis Su, Zhe Yang, Yang Wang, Shengru Zhao, Sen Zhao, Hengqiang Li, Xiaoxin Niu, Yuchen Qiu, Guixing Wu, Zhihong Wu, Nan Zhang, Terry Jianguo Genes (Basel) Article Depletion of ptk7 is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of PTK7 has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of PTK7 in 583 patients with CS and 302 patients with AIS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study. We identified a total of four rare variants in CS and four variants in AIS, including one protein truncating variant (c.464_465delAC) in a patient with CS. We then explored the effects of these variants on protein expression and sub-cellular location. We confirmed that the c.464_465delAC variant causes loss-of-function (LoF) of PTK7. In addition, the c.353C>T and c.2290G>A variants identified in two patients with AIS led to reduced protein expression of PTK7 as compared to that of the wild type. In conclusion, LoF and hypomorphic variants are associated with CS and AIS, respectively. MDPI 2021-11-12 /pmc/articles/PMC8619039/ /pubmed/34828397 http://dx.doi.org/10.3390/genes12111791 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 Su, Zhe Yang, Yang Wang, Shengru Zhao, Sen Zhao, Hengqiang Li, Xiaoxin Niu, Yuchen Qiu, Guixing Wu, Zhihong Wu, Nan Zhang, Terry Jianguo The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis |
title | The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis |
title_full | The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis |
title_fullStr | The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis |
title_full_unstemmed | The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis |
title_short | The Mutational Landscape of PTK7 in Congenital Scoliosis and Adolescent Idiopathic Scoliosis |
title_sort | mutational landscape of ptk7 in congenital scoliosis and adolescent idiopathic scoliosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619039/ https://www.ncbi.nlm.nih.gov/pubmed/34828397 http://dx.doi.org/10.3390/genes12111791 |
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