鉴定与胎儿重度脑缺血和硬膜下出血相关的 COL4A2 基因内含子变异。

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY BMC Medical Genomics Pub Date : 2024-09-30 DOI:10.1186/s12920-024-02012-4
Rong-Yue Sun, Yue Xu, Qing-Qing Huang, Si-Si Hu, Hua-Zhi Xu, Yan-Zhao Luo, Ting Zhu, Jun-Hui Sun, Yu-Jing Gong, Mian-Mian Zhu, Hong-Wei Wang, Jing-Ye Pan, Chao-Sheng Lu, Dan Wang
{"title":"鉴定与胎儿重度脑缺血和硬膜下出血相关的 COL4A2 基因内含子变异。","authors":"Rong-Yue Sun, Yue Xu, Qing-Qing Huang, Si-Si Hu, Hua-Zhi Xu, Yan-Zhao Luo, Ting Zhu, Jun-Hui Sun, Yu-Jing Gong, Mian-Mian Zhu, Hong-Wei Wang, Jing-Ye Pan, Chao-Sheng Lu, Dan Wang","doi":"10.1186/s12920-024-02012-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441077/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage.\",\"authors\":\"Rong-Yue Sun, Yue Xu, Qing-Qing Huang, Si-Si Hu, Hua-Zhi Xu, Yan-Zhao Luo, Ting Zhu, Jun-Hui Sun, Yu-Jing Gong, Mian-Mian Zhu, Hong-Wei Wang, Jing-Ye Pan, Chao-Sheng Lu, Dan Wang\",\"doi\":\"10.1186/s12920-024-02012-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":8915,\"journal\":{\"name\":\"BMC Medical Genomics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441077/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Medical Genomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12920-024-02012-4\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medical Genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12920-024-02012-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

背景:与 COL4A1 基因变异相比,COL4A2 基因变异并不常见,而且其胎儿临床表型迄今尚未得到很好的描述。我们报告了一名来自中国、患有 COL4A2 内含子变异、产前诊断为重度脑室畸形和硬膜下出血的胎儿:方法:应用全外显子组测序(WES)筛选潜在的遗传原因。方法:应用全外显子组测序(WES)筛选潜在的遗传病因,并通过生物信息学分析预测变异体的致病性。在体外实验中,进行了迷你基因检测以评估变异体的影响:结果:在该患者身上,我们观察到脑室肿大、硬膜下出血和广泛的脑畸形,初步认为是脑缺氧缺血性和/或出血性病变。WES发现了COL4A2基因中的一个新发杂合变异c.549 + 5G > A。这一新型变异导致第 8 号外显子的跳过,从而引起 24 个原生氨基酸的缺失,导致 COL4A2 蛋白缩短(p.Pro161_Gly184del):我们的研究表明,COL4A2 基因中的 c.549 + 5G > A 是一种通过异常剪接致病的变异。这一发现丰富了 COL4A2 基因的变异谱,不仅从临床角度提高了对缺氧缺血性病变相关胎儿神经系统疾病的认识,也为遗传诊断和咨询提供了指导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage.

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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
期刊最新文献
The signature of SARS-CoV-2-related genes predicts the immune therapeutic response and prognosis in breast cancer. Association between venous thromboembolism and atrial fibrillation: a Mendelian randomization study. New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis. RNA-seq validation of microRNA expression signatures for precision melanoma diagnosis and prognostic stratification. The Toll-like receptor 4 antagonist TAK-242 in combination with sodium hyaluronate alleviates postoperative abdominal adhesion in a mouse model.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1