{"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":"17 1","pages":"238"},"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\":\"17 1\",\"pages\":\"238\"},\"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}
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.
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.