中国家庭EVC变异的鉴定和植入前基因检测
Identification of EVC variants and the preimplantation genetic testing in a Chinese family.
摘要(中文译文)
胎儿遗传性骨骼疾病是常见的先天性异常，具有显著的遗传和表型异质性。遗传学分析在这些骨骼疾病的明确诊断中发挥着重要作用。本研究旨在确定一个中国家庭中，经孕中期常规产前超声检查发现的胎儿短肢（股骨长度<-2.0个标准差）骨骼疾病的致病遗传因素。全外显子组测序（WES）分析在患病胎儿中鉴定出EVC基因的杂合变异，包括一个既往未报道的移码变异（NM_153717.2: c.130del）和一个既往已报道的变异（NM_153717.2: c.1099_1563del）。结合遗传学和临床信息，该患病胎儿被诊断为Ellis-van Creveld（EVC，OMIM 225500）综合征。采用定量逆转录PCR（RT-qPCR）和Western blot分析评估了该既往未报道变异对mRNA和蛋白表达的功能影响。RT-qPCR分析显示，c.130del变异未影响EVC基因的转录表达，提示可能不存在无义介导的mRNA降解（NMD）。相反，Western blot分析显示截短蛋白异构体的积累，表明其在致病机制中可能发挥作用。该家庭接受了胚胎植入前遗传学检测（PGT），以获得未患EVC综合征或染色体非整倍体的婴儿。本研究鉴定并表征了EVC基因中一个既往未报道的变异，拓宽了已建立的突变谱，并对受EVC综合征影响家庭的临床管理和遗传咨询具有显著意义。
Abstract
Fetal genetic skeletal disorders are common congenital anomalies with notable genetic and phenotypic heterogeneity. Genetic analysis plays an important role in the definitive diagnosis of these skeletal conditions. In the present study, we aimed to determine the causative genetic factors underlying fetal skeletal disorders with shortened limbs (femoral lengths <-2.0 standard deviations) detected by routine second-trimester prenatal ultrasonography in a Chinese family. Whole exome sequencing (WES) analysis identified heterozygous variants in EVC in the affected fetus, including a previously unreported frameshift variant (NM_153717.2: c.130del) and a previously reported variant (NM_153717.2: c.1099_1563del). Combined genetic and clinical information indicated a diagnosis of Ellis-van Creveld (EVC, OMIM 225500) syndrome in the affected fetus. The functional impact of this previously unreported variant on mRNA and protein expression was assessed using quantitative reverse transcription PCR (RT-qPCR) and Western blot analysis. RT-qPCR analysis revealed that the c.130del variant did not affect the transcriptional expression of the EVC gene, suggesting the likely absence of nonsense-mediated mRNA decay (NMD). In contrast, Western blot analysis demonstrated the accumulation of truncated protein isoforms, indicating a potential role in the pathogenic mechanism. Preimplantation genetic testing (PGT) was performed on this family for a baby not affected by EVC syndrome or chromosomal aneuploidies. The present study identified and characterized a previously unreported variant in the EVC gene, which has broadened the established mutational spectrum and held notable implications for the clinical management and genetic counseling of families affected by EVC syndrome.
如何引用
AMA
Haiyan Luo, Zhen Guo, Yao Yu, Jia Chen, Qing Lu, Yan Yang, et al. Identification of EVC variants and the preimplantation genetic testing in a Chinese family.. Frontiers in medicine. 2026; doi:10.3389/fmed.2026.1798913.
APA
Haiyan Luo, Zhen Guo, Yao Yu, Jia Chen, Qing Lu, Yan Yang, et al (2026). Identification of EVC variants and the preimplantation genetic testing in a Chinese family.. Frontiers in medicine. https://doi.org/10.3389/fmed.2026.1798913
GB/T 7714
Haiyan Luo, Zhen Guo, Yao Yu, Jia Chen, Qing Lu, Yan Yang, et al. Identification of EVC variants and the preimplantation genetic testing in a Chinese family.[J]. Frontiers in medicine, 2026 doi:10.3389/fmed.2026.1798913.
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