Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage

doi:10.1186/s12920-024-02012-4

科研成果详情

题名	Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage
作者	Sun, Rong-Yue1; Xu, Yue1; Huang, Qing-Qing1; Hu, Si-Si 1; Xu, Hua-Zhi2; Luo, Yan-Zhao 3; Zhu, Ting 1; Sun, Jun-Hui4; Gong, Yu-Jing1; Zhu, Mian-Mian 1; Wang, Hong-Wei 5; Pan, Jing-Ye6,7; Lu, Chao-Sheng1; Wang, Dan 1
发表日期	2024-09-30
发表期刊	BMC Medical Genomics 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Heterozygous intronic variant Minigene splicing assays Encephalomalacia
其他关键词	COLLAGEN-IV ; MUTATIONS ; PHENOTYPE ; NEPHROPATHY
摘要	Background Genetic variants in COL4A2 are less common than those of COL4A1 and their fetal clinical phenotype has not been well described to date. We present a fetus from China with an intronic variant in COL4A2 associated with a prenatal diagnosis of severe cerebral encephalomalacia and subdural hemorrhage. Methods Whole exome sequencing (WES) was applied to screen potential genetic causes. Bioinformatic analysis was performed to predict the pathogenicity of the variant. In in vitro experiment, the minigene assays were performed to assess the variant's effect. Results In this proband, we observed ventriculomegaly, subdural hemorrhage, and extensive encephalomalacia that initially suggested cerebral hypoxic-ischemic and/or hemorrhagic lesions. WES identified a de novo heterozygous variant c.549 + 5G > A in COL4A2 gene. This novel variant leads to the skipping of exon 8, which induces the loss of 24 native amino acids, resulting in a shortened COL4A2 protein (p.Pro161_Gly184del). Conclusion Our study demonstrated that c.549 + 5G > A in COL4A2 gene is a disease-causing variant by aberrant splicing. This finding enriches the variant spectrum of COL4A2 gene, which not only improves the understanding of the fetal neurological disorders associated with hypoxic-ischemic and hemorrhagic lesions from a clinical perspective but also provides guidance on genetic diagnosis and counseling.
资助项目	National Natural Science Foundation of China
出版者	BMC
ISSN	1755-8794
EISSN	1755-8794
卷号	17 期号:1
DOI	10.1186/s12920-024-02012-4
页数	11
WOS类目	Genetics & Heredity
WOS研究方向	Genetics & Heredity
WOS记录号	WOS:001325776000001
收录类别	SCIE ; SCOPUS
URL	查看原文
PubMed ID	39350129
SCOPUSEID	2-s2.0-85205446233
通讯作者地址	[Lu, Chao-Sheng;Wang, Dan]Wenzhou Med Univ, Affiliated Hosp 1, Dept Pediat, 2 Fuxue Rd, Wenzhou 325000, Zhejiang, Peoples R China.
Scopus学科分类	Genetics;Genetics (clinical)
SCOPUS_ID	SCOPUS_ID:85205446233
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/220728
专题	附属第一医院附属第一医院_儿科附属第一医院_生殖医学中心
通讯作者	Lu, Chao-Sheng; Wang, Dan
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Dept Pediat, 2 Fuxue Rd, Wenzhou 325000, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Dept Radiol, Wenzhou, Zhejiang, Peoples R China; 3.Lishui Peoples Hosp, Dept Pediat, Lishui, Zhejiang, Peoples R China; 4.Wenzhou Med Univ, Affiliated Hosp 1, Reprod Med Ctr, Wenzhou, Zhejiang, Peoples R China; 5.Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Dis, Wenzhou, Zhejiang, Peoples R China; 6.Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Intelligent Treatment & Life Support Crit, Wenzhou, Zhejiang, Peoples R China; 7.Zhejiang Engn Res Ctr Hosp Emergency & Proc Digiti, 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
推荐引用方式 GB/T 7714	Sun, Rong-Yue,Xu, Yue,Huang, Qing-Qing,et al. Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage[J]. BMC Medical Genomics,2024,17(1).
APA	Sun, Rong-Yue., Xu, Yue., Huang, Qing-Qing., Hu, Si-Si., Xu, Hua-Zhi., ... & Wang, Dan. (2024). Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage. BMC Medical Genomics, 17(1).
MLA	Sun, Rong-Yue,et al."Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage".BMC Medical Genomics 17.1(2024).