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
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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。
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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.

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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.
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