Identification and functional characteristics of a novel splicing heterozygote variant of COL2A1 associated with Stickler syndrome type I

doi:10.3389/fgene.2024.1308737

科研成果详情

题名	Identification and functional characteristics of a novel splicing heterozygote variant of COL2A1 associated with Stickler syndrome type I
作者	Gong, Yujing1; Zhu, Weijian 2; Zhu, Mianmian 1; Chen, Dan 1,3; Wu, Sunke1,4; Hu, Sisi 1; Luo, Yi1,4; Jiang, Yiyi5; Zhu, Ting1; Wang, Dan 1
发表日期	2024-07-10
发表期刊	FRONTIERS IN GENETICS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Stickler syndrome functional analysis intron heterozygote variant type II collagenopathies
其他关键词	MUTATIONS ; GENETICS
摘要	Background: Stickler syndrome type I (STL1) is an autosomal dominant disorder characterized by ocular, auditory, orofacial, and skeletal anomalies. The main causes of STL1 are variants in the COL2A1 gene, which encodes a type II collagen precursor protein. The specific focus of this study was on a newborn from China diagnosed with STL1, with the aim of providing novel insights into the effects of a newly identified intronic variant in the COL2A1 gene on pre-mRNA splicing. Methods: Trio whole exome sequencing was used to identify the causative variant in the family. The identified variant was validated using Sanger sequencing. Bioinformatics programs were used to predict the pathogenicity of the candidate variant. Additionally, an in vitro minigene assay was used to investigate the effects of the identified variant on RNA splicing. Results: The proband with STL1 had a novel heterozygous splicing variant in the intron nine acceptor donor site of COL2A1 (c.655-2A>G). This splice junction variant resulted in aberrant COL2A1 mRNA splicing, leading to the skipping of exon 10 and the production of a shorter protein that may lack the last 18 native amino acids. Conclusion: The c.655-2A>G variant in the COL2A1 gene leads to STL1 through abnormal splicing. By expanding the spectrum of variants in the COL2A1 gene, this finding improves the clinical understanding of STL1 and provides guidance for early diagnosis and disease counseling.
资助项目	Zhejiang Medical Association [2020ZYC-B23]; National Natural Science Foundation of China [82171701]
出版者	FRONTIERS MEDIA SA
ISSN	1664-8021
EISSN	1664-8021
卷号	15
DOI	10.3389/fgene.2024.1308737
页数	10
WOS类目	Genetics & Heredity
WOS研究方向	Genetics & Heredity
WOS记录号	WOS:001275021400001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39050257
SCOPUSEID	2-s2.0-85199327922
通讯作者地址	[Wang, Dan]Wenzhou Med Univ, Affiliated Hosp 1, Dept Pediat, Wenzhou, Zhejiang, Peoples R China.
Scopus学科分类	Molecular Medicine;Genetics;Genetics (clinical)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/216824
专题	附属第一医院_儿科附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
通讯作者	Wang, Dan
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Dept Pediat, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Cent Lab, Wenzhou, Zhejiang, Peoples R China; 3.Yongjia Peoples Hosp, Dept Pediat, Wenzhou, Zhejiang, Peoples R China; 4.Taizhou Woman & Childrens Hosp, Dept Pediat, Taizhou, Zhejiang, Peoples R China; 5.Wenzhou Med Univ, Affiliated Hosp 1, Dept Radiog, Wenzhou, Zhejiang, Peoples R China
第一作者单位	附属第一医院_儿科
通讯作者单位	附属第一医院_儿科
第一作者的第一单位	附属第一医院_儿科
推荐引用方式 GB/T 7714	Gong, Yujing,Zhu, Weijian,Zhu, Mianmian,et al. Identification and functional characteristics of a novel splicing heterozygote variant of COL2A1 associated with Stickler syndrome type I[J]. FRONTIERS IN GENETICS,2024,15.
APA	Gong, Yujing., Zhu, Weijian., Zhu, Mianmian., Chen, Dan., Wu, Sunke., ... & Wang, Dan. (2024). Identification and functional characteristics of a novel splicing heterozygote variant of COL2A1 associated with Stickler syndrome type I. FRONTIERS IN GENETICS, 15.
MLA	Gong, Yujing,et al."Identification and functional characteristics of a novel splicing heterozygote variant of COL2A1 associated with Stickler syndrome type I".FRONTIERS IN GENETICS 15(2024).