Abstract：
OBJECTIVE: To carry out prenatal diagnosis for a fetus with Meckel syndrome (MKS) and explore its genetic basis.
METHODS: A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing.
RESULTS: The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c.296delA (p.Lys99SerfsTer6) and c.1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.296delA variant was predicted to be pathogenic (PVS1+PM2_Supporting+PP4), whilst the c.1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4).
CONCLUSIONS: The c.296delA and c.1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.
METHODS: A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing.
RESULTS: The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c.296delA (p.Lys99SerfsTer6) and c.1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.296delA variant was predicted to be pathogenic (PVS1+PM2_Supporting+PP4), whilst the c.1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4).
CONCLUSIONS: The c.296delA and c.1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.
摘要：
目的：对一例Meckel综合征(MKS)胎儿进行产前诊断并探讨其遗传基础。
方法：选择2018年2月在苏州市立医院就诊的一名孕妇作为研究对象。收集临床数据。收集流产的肌肉组织样本和夫妇的外周血样本。提取基因组DNA并进行染色体微阵列分析(CMA)和全外显子组测序。通过Sanger测序验证候选变体。
结果：发现胎儿患有小头畸形，羊水过少,妊娠18周时的多囊肾和香蕉状小脑。引产后,发现有脑膨出,肾囊肿和多指。CMA未发现异常。全外显子组测序揭示了新的复合杂合变体c.296delA（p。Lys99SerfsTer6）和c.1243G>A（p。Val415Met）在TMEM67基因中。根据美国医学遗传学和基因组学学院（ACMG）的指南，预测c.296delA变异是致病性的(PVS1+PM2_支持+PP4)，而预测c.1243G>A变体可能是致病性的(PM2_支持+PM3+PP3_中度+PP4)。
结论：c.296delA和c.1243G>TMEM67基因的复合杂合变体可能是该胎儿MKS的基础。
方法：选择2018年2月在苏州市立医院就诊的一名孕妇作为研究对象。收集临床数据。收集流产的肌肉组织样本和夫妇的外周血样本。提取基因组DNA并进行染色体微阵列分析(CMA)和全外显子组测序。通过Sanger测序验证候选变体。
结果：发现胎儿患有小头畸形，羊水过少,妊娠18周时的多囊肾和香蕉状小脑。引产后,发现有脑膨出,肾囊肿和多指。CMA未发现异常。全外显子组测序揭示了新的复合杂合变体c.296delA（p。Lys99SerfsTer6）和c.1243G>A（p。Val415Met）在TMEM67基因中。根据美国医学遗传学和基因组学学院（ACMG）的指南，预测c.296delA变异是致病性的(PVS1+PM2_支持+PP4)，而预测c.1243G>A变体可能是致病性的(PM2_支持+PM3+PP3_中度+PP4)。
结论：c.296delA和c.1243G>TMEM67基因的复合杂合变体可能是该胎儿MKS的基础。
