Department of Ultrasound Diagnosis, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
Mol Genet Genomic Med. 2021 Jul;9(7):e1710. doi: 10.1002/mgg3.1710. Epub 2021 May 20.
Neural tube defect (NTD) is a common birth defect causing much death in the world. Variants in VANGL1 lead to NTD and caudal regression syndrome. NTD displays a complex phenotype encompassing both genetic and environmental factors.
The fetus was diagnosed by prenatal ultrasound examination. Postnatal CT and autopsy were performed. Genetic testing was conducted in the family and Sanger sequencing was validated. Multiple prediction soft-wares were used to predict the pathogenicity of the variant.
The VANGL1 gene variant c.1151C>G (P384R) was detected in a fetus diagnosed with tethered spinal cord and sacrococcygeal lipoma. The VANGL1 variant c.1151C>G (P384R) was reported in a Klippel-Feil syndrome patient. The VANGL1 variant was validated in the trio-family but the mother showed no abnormalities.
Overall, this study presents fetal NTD caused by the same VANGL1 variant found in a Klippel-Feil syndrome patient with complete clinical information of prenatal ultrasound, postnatal CT, and genetic results as early as 25 GW. Our study not only expands the VANGL1 mutational spectrum but also sheds light on the important role of the VANGL1 P384R variant in human development.
神经管缺陷（NTD）是一种常见的出生缺陷，在世界范围内导致了大量死亡。VANGL1 变异导致 NTD 和尾退化综合征。NTD 表现出复杂的表型，包含遗传和环境因素。
通过产前超声检查诊断胎儿。进行产后 CT 和尸检。对家族进行基因检测，并验证 Sanger 测序。使用多种预测软件预测变异的致病性。
在诊断为脊髓栓系和骶尾部脂肪瘤的胎儿中检测到 VANGL1 基因变异 c.1151C>G（P384R）。VANGL1 变异 c.1151C>G（P384R）在 Klippel-Feil 综合征患者中报道过。VANGL1 变异在三人家族中得到验证，但母亲没有异常。
总的来说，本研究报告了胎儿 NTD 是由 Klippel-Feil 综合征患者中相同的 VANGL1 变异引起的，该患者具有完整的产前超声、产后 CT 和遗传结果的临床信息，最早在 25GW 时发现。我们的研究不仅扩展了 VANGL1 突变谱，还揭示了 VANGL1 P384R 变异在人类发育中的重要作用。
