A novel nonsense mutation in the L1CAM gene responsible for X-linked congenital hydrocephalus
A novel nonsense mutation in the L1CAM gene responsible for X-linked congenital hydrocephalus
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L1CAM 基因中一种新的无义突变导致 X 连锁先天性脑积水
DOI：
10.1002/jgm.3180
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发表时间：
2020-03-30
影响因子：
3.5
通讯作者：
Yao, Ruojin
中科院分区：
文献类型：
--
作者：
Guo, Dewei;Shi, Yuting;Yao, Ruojin
背景先天性脑积水是对多种原因引起的症状的描述性诊断，这些症状包括染色体异常、基因突变、宫内感染和出血等。L1CAM基因突变是先天性脑积水最常见的原因，约占X-连锁先天性脑积水的30%。方法采用全外显子组测序和Sanger测序的方法，研究了一例流产的男性胎儿，其母亲有两次因脑积水而自愿终止妊娠的病史。结果胎儿全外显子测序及变异分离分析发现，L1CAM基因第21外显子(NM_000425.4)存在一种新的母系来源的半合子无义突变(c.2865G>；A；p.Y955*)。观察到严重的脑积水，并伴有明显的侧脑室扩张。侧脑室壁表面的电子显微照片显示室管膜纤毛缺失。结论本研究建议对有孤立性脑积水的男性胎儿，特别是有家族史的男性胎儿，应考虑进行L1CAM基因突变筛查，以利于后续妊娠的产前诊断。
Background Congenital hydrocephalus is a descriptive diagnosis of symptoms, that are present for numerous reasons, including chromosomal disorders, genetic mutations, intrauterine infection and hemorrhage, amongst other factors. Mutation of L1CAM gene is the most frequent cause of congenital hydrocephalus, contributing to approximately 30% of X-linked congenital hydrocephalus.Methods In the present study, we used whole-exome sequencing and Sanger sequencing to investigate an aborted male fetus present with severe congenital hydrocephalus at 24 weeks of gestation, whose mother had a history of two previous voluntary terminations of pregnancies as a result of hydrocephalus. Magnetic resonance imaging, an autopsy and electron microscopy were performed and the phenotypic changes were described.Results Whole-exome sequencing in the fetus, as well as variant segregation analysis, revealed a novel maternally derived hemizygous nonsense mutation (c.2865G>A; p. Y955*) in exon 21 of the L1CAM gene (NM_000425.4). Severe hydrocephalus was observed along with marked dilatation of lateral ventricles. An electron micrograph of the surface of lateral ventricle walls revealed a lack of ependymal cilia.Conclusion The present study suggests that L1CAM mutation screening should be considered for a male fetus with isolated hydrocephalus, especially with a family history, which could facilitate prenatal diagnosis in a subsequent pregnancy.