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 investig...

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Autores principales:	Zhe Su, Yang Yang, Shengru Wang, Sen Zhao, Hengqiang Zhao, Xiaoxin Li, Yuchen Niu, Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) Study Group, Guixing Qiu, Zhihong Wu, Nan Wu, Terry Jianguo Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	protein tyrosine kinase 7 (<i>PTK7</i>) congenital scoliosis adolescent idiopathic scoliosis whole exome sequencing Genetics QH426-470
Acceso en línea:	https://doaj.org/article/09d891cf3fac4b77a9a53608bbd62e87
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spelling	oai:doaj.org-article:09d891cf3fac4b77a9a53608bbd62e872021-11-25T17:42:00ZThe Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis10.3390/genes121117912073-4425https://doaj.org/article/09d891cf3fac4b77a9a53608bbd62e872021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1791https://doaj.org/toc/2073-4425Depletion of <i>ptk7</i> is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of <i>PTK7</i> has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of <i>PTK7</i> 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 <i>PTK7</i>. 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.Zhe SuYang YangShengru WangSen ZhaoHengqiang ZhaoXiaoxin LiYuchen NiuDeciphering Disorders Involving Scoliosis and COmorbidities (DISCO) Study GroupGuixing QiuZhihong WuNan WuTerry Jianguo ZhangMDPI AGarticleprotein tyrosine kinase 7 (<i>PTK7</i>)congenital scoliosisadolescent idiopathic scoliosiswhole exome sequencingGeneticsQH426-470ENGenes, Vol 12, Iss 1791, p 1791 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	protein tyrosine kinase 7 (<i>PTK7</i>) congenital scoliosis adolescent idiopathic scoliosis whole exome sequencing Genetics QH426-470
spellingShingle	protein tyrosine kinase 7 (<i>PTK7</i>) congenital scoliosis adolescent idiopathic scoliosis whole exome sequencing Genetics QH426-470 Zhe Su Yang Yang Shengru Wang Sen Zhao Hengqiang Zhao Xiaoxin Li Yuchen Niu Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) Study Group Guixing Qiu Zhihong Wu Nan Wu Terry Jianguo Zhang The Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis
description	Depletion of <i>ptk7</i> is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of <i>PTK7</i> has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of <i>PTK7</i> 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 <i>PTK7</i>. 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	article
author	Zhe Su Yang Yang Shengru Wang Sen Zhao Hengqiang Zhao Xiaoxin Li Yuchen Niu Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) Study Group Guixing Qiu Zhihong Wu Nan Wu Terry Jianguo Zhang
author_facet	Zhe Su Yang Yang Shengru Wang Sen Zhao Hengqiang Zhao Xiaoxin Li Yuchen Niu Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) Study Group Guixing Qiu Zhihong Wu Nan Wu Terry Jianguo Zhang
author_sort	Zhe Su
title	The Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis
title_short	The Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis
title_full	The Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis
title_fullStr	The Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis
title_full_unstemmed	The Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis
title_sort	mutational landscape of <i>ptk7</i> in congenital scoliosis and adolescent idiopathic scoliosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/09d891cf3fac4b77a9a53608bbd62e87
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The Mutational Landscape of <i>PTK7</i> in Congenital Scoliosis and Adolescent Idiopathic Scoliosis

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