Prenatal diagnosis of a case with Schuurs-Hoeijmakers syndrome
苏利沙 1朱晓帆 1吴庆华 1孔祥东 1许芯
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作者信息
1. 郑州大学第一附属医院遗传与产前诊断中心，郑州 450052
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摘要
目的 探讨1例Schuurs-Hoeijmakers综合征(SHS)胎儿的遗传学病因，为其产前诊断提供依据。 方法 选取2021年3月20日因胎儿超声异常到郑州大学第一附属医院门诊进行咨询的1名孕妇及其胎儿作为研究对象，收集胎儿临床资料和超声检查结果。羊膜腔穿刺获得胎儿羊水细胞进行常规G显带染色体核型分析及低深度全基因组拷贝数变异(CNV)检测(CNV-seq)，全外显子组测序(WES)筛查胎儿可疑致病基因变异，Sanger测序进行家系验证。 结果 胎儿在胎龄21+5周超声提示颈后皱褶增厚(9.0 mm)，双肾实质回声增强，腹腔积液，左侧胸腔积液，右移心。孕妇既往1次妊娠胎儿多发畸形。胎儿羊水细胞染色体核型分析和CNV-seq检测结果均未见异常。WES提示胎儿携带PACS1基因c.607C>T(p.Arg203Trp)杂合变异，Sanger测序验证提示该变异为新发变异。根据ACMG变异评级指南，c.607C>T(p.Arg203Trp)变异评级为疑似致病变异(PS2+PM2_Supporting+PP3)。 结论 PACS1基因c.607C>T(p.Arg203Trp)杂合变异是该SHS胎儿多发异常的遗传学病因。针对多发结构异常胎儿，CNV未发现异常情况下进行全外显子组测序能够提高胎儿遗传学病因检出率。 Objective To explore the genetic basis for a fetus with multiple malformations. Methods Clinical data of the fetus was collected, Amniotic fluid sample of the fetus was subjected to conventional G-banded karyotyping, low-depth whole genome copy number variants detection and whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing of the fetus and its parents. Results Prenatal ultrasound scan at 21+ 5 gestational weeks had revealed increased nuchal thickness (9.0 mm), enhanced echos of bilateral renal parenchyma, seroperitoneum, left pleural effusion and right displacement of the heart. The mother had a previous history of terminated pregnancy for multiple fetal anomalies. No abnormality was found by conventional karyotyping and CNV analysis, though WES revealed that the fetus has harbored a de novo heterozygous c. 607C>T (p.Arg203Trp) variant of theACS1 gene (NM_018026.3), and the result was validated by Sanger sequencing. Conclusion Through WES and prenatal ultrasonography, the fetus was diagnosed with Schuurs-Hoeijmakers syndrome due to the heterozygous c. 607C>T (p.Arg203Trp) variant of thePACS1 gene (NM_018026.3). For fetuses with multiple malformations, WES can help to reveal the genetic etiology when CNV result is negative.
Abstract
Objective To explore the genetic basis for a fetus with multiple malformations. Methods Clinical data of the fetus was collected, Amniotic fluid sample of the fetus was subjected to conventional G-banded karyotyping, low-depth whole genome copy number variants detection and whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing of the fetus and its parents. Results Prenatal ultrasound scan at 21+ 5 gestational weeks had revealed increased nuchal thickness (9.0 mm), enhanced echos of bilateral renal parenchyma, seroperitoneum, left pleural effusion and right displacement of the heart. The mother had a previous history of terminated pregnancy for multiple fetal anomalies. No abnormality was found by conventional karyotyping and CNV analysis, though WES revealed that the fetus has harbored a de novo heterozygous c. 607C>T (p.Arg203Trp) variant of theACS1 gene (NM_018026.3), and the result was validated by Sanger sequencing. Conclusion Through WES and prenatal ultrasonography, the fetus was diagnosed with Schuurs-Hoeijmakers syndrome due to the heterozygous c. 607C>T (p.Arg203Trp) variant of thePACS1 gene (NM_018026.3). For fetuses with multiple malformations, WES can help to reveal the genetic etiology when CNV result is negative.
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