Zhuang Jianlong, Chen Chunnuan, Wang Yuanbai, Zeng Shuhong, Chen Yu'e, Jiang Yuying, Xie Yingjun, Wang Gaoxiong
Prenatal Diagnosis Center, Quanzhou Women's and Children's Hospital, Quanzhou, China.
Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Front Genet. 2022 Jul 5;13:924573. doi: 10.3389/fgene.2022.924573. eCollection 2022.
Pathogenic mutations in the gene were associated with long QT syndrome 2 (LQT2), which typically manifest in a prolonged QT interval and may lead to recurrent syncopes, seizure, or sudden death. Limited reports indicated that the mutations would result in LQT2 combined with tetralogy of fallot. Our goal was to present an additional case of LQT2 combined with the tetralogy of fallot in a fetus with a novel mutation. Enrolled in this study was a 23-year-old pregnant woman from Quanzhou Fujian province, China. In her pregnancy, fetal ultrasound anomalies were identified, including tetralogy of fallot, coronary sinus enlargement, and persistent left superior vena cava. No chromosomal abnormality was detected by fetal karyotype analysis. However, 238.1-kb duplication in the 2q14.2 region containing the gene was observed in the fetus by chromosomal array analysis, which was inherited from the mother with normal clinical features and interpreted as a variant of uncertain significance (VOUS). Furthermore, whole-exome sequencing (WES) detection identified a novel nonsense c.1907C > G (p.S636*) mutation in the gene in the fetus, and it was classified as a likely pathogenic variant, according to the ACMG guidelines. Parental verification analysis indicated that c.1907C > G (p.S636*) mutation was inherited from the mother. In this study, we believe that 2q14.2 duplication may not be the reason for fetal heart defects; moreover, we described an additional case with gene mutation, which may lead to LQTS and be associated with congenital heart defects. In addition, our study further confirms the application value of the WES technology in prenatal genetic etiology diagnosis of fetuses with structural anomalies and unexplained structural variants.
该基因的致病性突变与长QT综合征2型（LQT2）相关，其通常表现为QT间期延长，并可能导致反复晕厥、癫痫发作或猝死。有限的报告表明，该突变会导致LQT2合并法洛四联症。我们的目标是报告一例胎儿LQT2合并法洛四联症且存在新型该基因突变的病例。本研究纳入了一名来自中国福建省泉州市的23岁孕妇。在孕期，通过胎儿超声检查发现了胎儿异常，包括法洛四联症、冠状窦扩大和永存左上腔静脉。胎儿核型分析未检测到染色体异常。然而，通过染色体微阵列分析在胎儿中观察到2q14.2区域存在包含该基因的238.1-kb重复，该重复遗传自临床特征正常的母亲，并被解释为意义未明的变异（VOUS）。此外，全外显子测序（WES）检测在胎儿该基因中鉴定出一个新型无义突变c.1907C > G（p.S636*），根据美国医学遗传学与基因组学学会（ACMG）指南，该突变被分类为可能的致病变异。亲代验证分析表明，c.1907C > G（p.S636*）突变遗传自母亲。在本研究中，我们认为2q14.2重复可能不是胎儿心脏缺陷的原因；此外，我们描述了另一例存在该基因突变的病例，该突变可能导致LQTS并与先天性心脏缺陷相关。此外，我们的研究进一步证实了WES技术在产前对具有结构异常和不明结构变异胎儿进行遗传病因诊断中的应用价值。
