首页|Walker-Warburg综合征胎儿1例的产前诊断

Walker-Warburg综合征胎儿1例的产前诊断

Prenatal diagnosis for a fetus with Walker-Warburg syndrome

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目的 探讨1例Walker-Warburg综合征(WWS)胎儿的遗传学特征。 方法 选取2021年6月9日至甘肃省妇幼保健院确诊的1例WWS胎儿为研究对象，采集胎儿羊水及其父母和姐姐的外周血样，提取基因组DNA，进行trio-WES检测，用Sanger测序对候选变异进行家系验证。 结果 Trio-WES检测显示胎儿POMT2基因存在第4外显子c.471delC(p.F158Lfs*42)移码变异和第20外显子的c.1975C>T(p.R659W)错义变异，分别遗传自父亲和母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南分别判定为致病性变异(PVS1+PM2_Supporting+PP4)和可能致病性变异(PM2_Supporting+PM3+PP3_Moderate+PP4)。 结论 产前诊断中应用trio-WES检测可快速可靠的确诊WWS患儿，为临床决策发挥重要作用。同时，发现POMT1基因1种新变异，在国内外未见报道。扩充了POMT2基因致病变异谱，为疾病的临床诊断和遗传咨询提供理论依据。 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). Conclusion 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.
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). Conclusion 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.

Walker-Warburg syndromePOMT2 geneHydrocephalusLateral ventricle wideningBioinformatics analysis

马盼盼、陈雪、惠玲、张庆华、张钏、郝胜菊、杨兰、王兴、徐福蓉、周秉博、李岭

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甘肃省妇幼保健院医学遗传中心　甘肃省出生缺陷与罕见病临床研究中心，兰州　730050

Walker-Warburg综合征 POMT2基因 脑积水 侧脑室增宽 生物信息学分析

国家重点研发计划甘肃省科技计划甘肃省科技计划甘肃省妇幼保健院重大攻关项目(2021)甘肃省科技计划民生科技专项兰州市科技计划

2018YFC100250421JR7RA68021JR1RA04520CX4FA0032021-1-182

2023

10.3760/cma.j.cn511374-20220425-00279

中华医学遗传学杂志
中华医学会

中华医学遗传学杂志

CSTPCDCSCD
影响因子：0.562
ISSN：1003-9406
年,卷(期)：2023.40(5)
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