A Novel Silent Mutation in the L1CAM Gene causing Fetal Hydrocephalus
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PROVIDER: PRJNA549864 | ENA |
REPOSITORIES: ENA
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Project description:To explore the genetic cause of a Chinese woman with fetal hydrocephalus X-linked hydrocephalus (XLH), a genetic disorder, has an incidence of 1/30,000 male births. The great proportion of XLH is ascribed to loss of function mutations of L1 cell adhesion molecule gene (L1CAM), but silent mutations in L1CAM with pathogenic potential were rare, and were usually ignored especially in WES detection. In the present study, we describe a novel silent L1CAM mutation in a Chinese pregnant woman reporting continuous five times pregnancies with fetal hydrocephalus. After fetal blood sampling, we found c.453G>T (p.Gly151=) in L1CAM gene of the fetus by whole exome sequencing (WES), RT-PCR of the mRNA from cord blood mononuclear cells and subsequent sequence analysis identified the mutation created a potential 5' splice site consensus sequence, which would result in an in-frame deletion of 72 bp from exon 5 and 24 amino acids of the L1CAM protein. Heterozygous mutations were confirmed in analyzing DNA and mRNA from peripheral blood mononuclear cells of the woman, and, a severe L1 syndrome was confirmed by fetal ultrasound scan and MRI. Our study first indicated c.453G>T (p.Gly151=) in L1CAM could be disease causing for hydrocephalus, which would aid in genetic counseling for the prenatal diagnosis of hydrocephalus. Meanwhile, it suggested some silent mutations detected in WES should not be ignored, splicing predictions of these mutations were necessary.
2019-07-16 | GSE133063 | GEO
Project description:We studies on how a hydrocephalus-causing mutation (R783H) on Trim71 alters Trim71's substrate mRNA binding
2022-11-04 | GSE183715 | GEO
Project description:We studies on how a hydrocephalus-causing mutation (R783H) on mouse Trim71 alters transcriptomes in mouse embryonic stem cells
2022-11-04 | GSE196017 | GEO
Project description:X-linked hydrocephalus (XLH), a genetic disorder, has an incidence of 1/30,000 male births. The great proportion of XLH is ascribed to loss-of-function mutations of L1 cell adhesion molecule gene (L1CAM), but silent mutations in L1CAM with pathogenic potential were rare and were usually ignored especially in whole-exome sequencing (WES) detection. In the present study, we describe a novel silent L1CAM mutation in a Chinese pregnant woman reporting continuous five times pregnancies with fetal hydrocephalus. After fetal blood sampling, we found c.453G > T (p.Gly151 = ) in the L1CAM gene of the fetus by WES; RT-PCR of the messenger RNA (mRNA) from cord blood mononuclear cells and subsequent sequence analysis identified the mutation created a potential 5' splice site consensus sequence, which would result in an in-frame deletion of 72 bp from exon 5 and 24 amino acids of the L1CAM protein. Heterozygous mutations were confirmed in analyzing DNA and mRNA from peripheral blood mononuclear cells of the woman, and a severe L1 syndrome was confirmed by fetal ultrasound scan and MRI. Our study first indicated c.453G > T (p.Gly151 = ) in L1CAM could be disease causing for hydrocephalus, which would aid in genetic counseling for the prenatal diagnosis of hydrocephalus. Meanwhile, it suggested some silent mutations detected in WES should not be ignored; splicing predictions of these mutations were necessary.
| S-EPMC6749797 | biostudies-literature
Project description:Studies on a hydrocephalus-causing mutation on Trim71
| PRJNA761727 | ENA
Project description:Studies on a hydrocephalus-causing mutation on Trim71 [RNA-seq]
| PRJNA802914 | ENA
Project description:We studies on how a hydrocephalus-associated mutation (R595H) on Trim71 alters Trim71's substrate mRNA binding
2022-05-07 | GSE201945 | GEO
Project description:Transcriptional profiling of the parietal cortex was performed in postnatal day 22 rats with obstructive hydrocephalus. An intracisternal injection of kaolin was done on postnatal day one, and severe hydrocephalus developed over 3 weeks. Hydrocephalic animals were compared to age-matched saline controls. The goal was to determine the effects of kaolin-induced neonatal hydrocephalus on gene expression. Two-condition experiment: kaolin-induced vs. saline-injected controls. Replicates: 5 treatment samples and 5 saline controls.
2010-07-30 | E-GEOD-16985 | biostudies-arrayexpress
Project description:BackgroundX-linked hydrocephalus (XLH), characterized by mental retardation and bilateral adducted thumbs, often come out to be a genetic disorder of L1CAM. It codes the protein L1 cell adhesion molecule (L1CAM), playing a crucial role in the development of the nervous system. The objective of the study was to report a new disease-causing mutation site of L1CAM, and gain further insight into the pathophysiology of hydrocephalus.MethodsWe collect the samples of a couple and their second hydrocephalic fetus. Then, the whole-exome sequencing and in-depth mutation analysis were performed.ResultsThe variant c.2491delG (p.V831fs), located in the exon 19 of L1CAM (chrX:153131214), could damage the L1CAM function by producing a frameshift in the translation of fibronectin type-III of L1CAM.ConclusionWe identified a novel disease-causing mutation in L1CAM for the first time, which further confirmed L1CAM as a gene underlying XLH cases.
| S-EPMC6978236 | biostudies-literature