A New Splicing Mutation in the L1CAM Gene Responsible for X-Linked Hydrocephalus (HSAS)
A New Splicing Mutation in the L1CAM Gene Responsible for X-Linked Hydrocephalus (HSAS)
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DOI：
10.1007/s12031-016-0754-3
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发表时间：
2016-07-01
影响因子：
3.1
通讯作者：
Gambardella, Stefano
中科院分区：
文献类型：
--
作者：
Ferese, Rosangela;Zampatti, Stefania;Gambardella, Stefano
X连锁脑积水（XLH）是一种遗传性疾病，导致一种以智力低下、双侧拇指内收、上肢和下肢痉挛为特征的综合征。在大多数情况下，X 连锁突变会导致神经元细胞粘附分子 L1CAM（L1 细胞粘附分子，OMIM 308840）活性缺陷。根据 L1CAM 的突变，已经描述了四种 X 连锁神经系统综合征。这些综合征非常不同，尽管每种综合征都具有显着的变异性。在本研究中，我们描述了一名 33 岁女性的一种新的 L1CAM 突变，该女性报告两次因胎儿脑积水自愿终止妊娠。遗传分析鉴定出潜在的剪接变异体c.1267+5delG。体外分析时，这种突变会导致外显子 10 的跳跃。第二次妊娠的羊水细胞 DNA 分析中也证实了同样的突变，超声扫描和尸检也证实了严重的 L1 综合征的发生。这些数据描述了一种新的 L1 突变，它提高了我们对基因型-表型相关性的理解，同时证实了 L1CAM 突变产前筛查的重要性。
X-linked hydrocephalus (XLH) is a genetic disorder leading to a syndrome characterized by mental retardation, bilateral adducted thumbs, and spasticity of upper and lower limbs. In most cases, X-linked mutation leads to a defective activity of the neuronal cell adhesion molecule L1CAM (L1 cell adhesion molecule, OMIM 308840). Depending on mutations of L1CAM, four X-linked neurological syndromes have been described. These syndromes are very different albeit each one possesses marked variability. In the present study, we describe a novel L1CAM mutation in a 33-year-old woman reporting two voluntary terminations of pregnancy due to fetal hydrocephalus. The genetic analysis identified the potential splicing variant c.1267+5delG. When analyzed in vitro, this mutation produces the skipping of exon 10. The same mutation was confirmed in analyzing DNA from amniocytes from the second pregnancy, and ultrasound scan and autopsy confirmed the occurrence of a severe L1 syndrome. These data describe a novel L1 mutation which improves our understanding on genotype-phenotype correlation while confirming the importance of prenatal screening for L1CAM mutations.