The Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Mol Genet Genomic Med. 2022 Sep;10(9):e2002. doi: 10.1002/mgg3.2002. Epub 2022 Jul 5.
The molecular mutations of the L1CAM gene and the imaging appearances of four fetuses with L1 syndrome from three independent Chinese families with a history of hydrocephalus were reported in this study. Two of the three are novel L1CAM variants.
Results of clinical and imaging examinations of three Chinese families were collected. Fetal samples were collected by puncture, genomic DNA was extracted, whole-exome sequencing was performed, and the L1CAM gene mutation sites were verified by PCR and Sanger sequencing.
In this case report, we described the imaging appearance and investigated the mutations of the L1CAM gene in three Chinese families with a history of L1 syndrome; these included two nonsense mutations (c.262C>T and c.261C>G) and one splice-site mutation (c.524-1G>A). Two of these three are novel L1CAM variants: c.262C>T and c.261C>G. The results of the sonographic images of the affected fetuses showed severe hydrocephalus. Bilateral lateral ventricles were dilated in the fetuses with c.262C>T and c.261C>G mutations. The left ventricle was about 14 mm wide and the right was about 14 mm in the fetus with c.262C>T mutation. The left ventricle was about 24.9 mm wide and the right was about 23.9 mm in the fetus with c.261C>G mutation. The ultrasound examination of the fetus with c.524-1G>A mutation showed that the third ventricle (7.5 mm wide) was raised, and the fourth ventricle was communicated with the cisterna magna. The parents requested termination of the above pregnancy.
The current study emphasizes the importance of combining family history, prenatal ultrasonography, and L1CAM mutation testing positive for the diagnosis of the L1 syndrome.
本研究报道了三个独立的中国 L1 综合征家系的 4 例 L1 综合征胎儿的 L1CAM 基因突变和影像学表现，其中 2 个为新的 L1CAM 变异。
收集了三个中国家系的临床和影像学检查结果。通过穿刺采集胎儿样本，提取基因组 DNA，进行全外显子组测序，并通过 PCR 和 Sanger 测序验证 L1CAM 基因突变位点。
在本病例报告中，我们描述了三个有 L1 综合征家族史的中国家庭的影像学表现和 L1CAM 基因突变情况；包括 2 个无义突变（c.262C>T 和 c.261C>G）和 1 个剪接位点突变（c.524-1G>A）。其中 2 个为新的 L1CAM 变异：c.262C>T 和 c.261C>G。受影响胎儿的超声图像结果显示严重脑积水。携带 c.262C>T 和 c.261C>G 突变的胎儿双侧侧脑室扩张。携带 c.262C>T 突变的胎儿左心室宽约 14mm，右心室宽约 14mm。携带 c.261C>G 突变的胎儿左心室宽约 24.9mm，右心室宽约 23.9mm。携带 c.524-1G>A 突变的胎儿超声检查显示第三脑室（7.5mm 宽）升高，第四脑室与小脑延髓池相通。上述妊娠的父母要求终止妊娠。
本研究强调了结合家族史、产前超声和 L1CAM 基因突变检测阳性对 L1 综合征诊断的重要性。
