Abstract：
OBJECTIVE: To explore the genetic etiology for a fetus with Walker-Warburg syndrome(WWS).
METHODS: A fetus with WWS diagnosed at Gansu Provincial Maternity and Child Health Care Hospital in June 9, 2021 was selected as the study subject. Genomic DNA was extracted from amniotic fluid sample of the fetus and peripheral blood samples from its parents. Trio-Whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing.
RESULTS: The fetus was found to harbor compound heterozygous variants of the POMT2 gene, namely c.471delC (p.F158Lfs*42) and c.1975C>T (p.R659W), which were respectively inherited from its father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively rated as pathogenic (PVS1+PM2_Supporting+PP4) and likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4).
CONCLUSIONS: Trio-WES may be used for the prenatal diagnosis of WWS. The compound heterozygous variants of the POMT2 gene probably underlay the disorder in this fetus. Above finding has expanded the mutational spectrum of the POMT2 gene and enabled definite diagnosis and genetic counseling for the family.
METHODS: A fetus with WWS diagnosed at Gansu Provincial Maternity and Child Health Care Hospital in June 9, 2021 was selected as the study subject. Genomic DNA was extracted from amniotic fluid sample of the fetus and peripheral blood samples from its parents. Trio-Whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing.
RESULTS: The fetus was found to harbor compound heterozygous variants of the POMT2 gene, namely c.471delC (p.F158Lfs*42) and c.1975C>T (p.R659W), which were respectively inherited from its father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively rated as pathogenic (PVS1+PM2_Supporting+PP4) and likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4).
CONCLUSIONS: Trio-WES may be used for the prenatal diagnosis of WWS. The compound heterozygous variants of the POMT2 gene probably underlay the disorder in this fetus. Above finding has expanded the mutational spectrum of the POMT2 gene and enabled definite diagnosis and genetic counseling for the family.
摘要：
目的：探讨Walker-Warburg综合征(WWS)胎儿的遗传学病因。
方法：选取2021年6月9日在甘肃省妇幼保健院确诊的WWS胎儿作为研究对象。从胎儿的羊水样品和其父母的外周血样品中提取基因组DNA。进行三全外显子组测序(trio-WES)。通过Sanger测序验证候选变体。
结果：发现胎儿携带POMT2基因的复合杂合变体，即c.471delC（p。F158Lfs*42）和c.1975C>T（p。R659W),分别从其父亲和母亲那里继承。根据美国医学遗传学和基因组学学院（ACMG）的指南，它们分别被评为致病性(PVS1+PM2_支持+PP4)和可能致病性(PM2_支持+PM3+PP3_中度+PP4)。
结论：Trio-WES可用于WWS的产前诊断。POMT2基因的复合杂合变体可能是该胎儿疾病的基础。上述发现扩大了POMT2基因的突变谱，并为该家族提供了明确的诊断和遗传咨询。
方法：选取2021年6月9日在甘肃省妇幼保健院确诊的WWS胎儿作为研究对象。从胎儿的羊水样品和其父母的外周血样品中提取基因组DNA。进行三全外显子组测序(trio-WES)。通过Sanger测序验证候选变体。
结果：发现胎儿携带POMT2基因的复合杂合变体，即c.471delC（p。F158Lfs*42）和c.1975C>T（p。R659W),分别从其父亲和母亲那里继承。根据美国医学遗传学和基因组学学院（ACMG）的指南，它们分别被评为致病性(PVS1+PM2_支持+PP4)和可能致病性(PM2_支持+PM3+PP3_中度+PP4)。
结论：Trio-WES可用于WWS的产前诊断。POMT2基因的复合杂合变体可能是该胎儿疾病的基础。上述发现扩大了POMT2基因的突变谱，并为该家族提供了明确的诊断和遗传咨询。
