A NOVEL MUTATION IN CYP2C9
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB40955 | ENA |
REPOSITORIES: ENA
Similar Datasets
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 identified a novel germline mutation of the microphthalmia-associated transcription factor (MITF - E318K). This mutation was found to be present in numerous melanoma families, as well as the general population, where its association with melanoma has a significant effect. We determined the effect of the E318K mutation on global MITF target gene transcription. We developed a tetracycline-inducible system for expression of wild type MITF or the E318K variant in melanoma cell lines with constitutively low or undetectable levels of endogenous MITF (HT144 and C32). We examined whole-genome expression profiles in these cells following induction of either wild-type or E318K MITF for 48 hours. Analysis suggests that the MITF E318K mutant exhibits differential transcriptional activity against some, though not all, target genes. Expression profiling by array
2011-12-01 | E-GEOD-31269 | biostudies-arrayexpress
Project description:POC1A encodes a WD repeat protein localizing to centrioles and spindle poles and associated with Short stature, onychodysplasia, facial dysmorphism and hypotrichosis (SOFT) syndrome (OMIM #614813). In our study, we reported on two patients with primordial dwarfism (PD) from the same family. We utilized Whole Exome Sequencing (WES) in the patients to screen all PD related genes and to define putative novel candidate genes. A novel homozygous p.T120A missense mutation was detected in POC1A, a known causative gene of SOFT syndrome, and confirmed using Sanger sequencing. To confirm the pathogenicity of the detected mutation, primary fibroblast cultures obtained from the patients and a control individual were used. Gene expression profiles of the fibroblast cultures were taken. We performed gene expression arrays on fibroblasts cultured from patients with SOFT syndrome and POC1A mutation and compared their expression profiles to that of control fibroblast cells.
2015-07-15 | E-GEOD-66314 | biostudies-arrayexpress
Project description:Background: In vitro models are an essential tool towards understanding the molecular characteristics of colorectal cancer (CRC) and the testing of therapies for CRC. To this end we established 21 novel CRC cell lines of which six were derived from liver metastases. Extensive genetic, genomic, transcriptomic and methylomic profiling was performed in order to characterize these new cell lines and all data is made publically available. Additionally, sensitivity of oxaliplatin was tested as a measure for chemotherapy resistance. Results: DNA copy-number alterations (CNA) were compared between primary and metastasis derived cell lines. In concordance with previous studies copy-number gain of chr20, and loss of chr8p were found highly specific for liver metastases. Previously reported BRAF-mutation associated DNA methylation profiles could be validated on the genome-wide DNA methylation profiles of these cell lines. 47.6% of the loci previously reported to associate with BRAF mutation status were reproduced in this dataset. When examining the gene expression profiles in conjunction with these DNA methylation results, we identified 20 genes of which the gene expression correlated with the DNA methylation status, including MEIS1, LRAT and STC2. These genes have previously been reported to be subject to transcriptional regulation through DNA hypermethylation, validating our approach. Conclusions: By combining mutation profiles with CNA and gene expression profiles we constructed an overview of the alterations in the major CRC-related signalling pathways. The mutation profiles, along with the genome, transcriptome and methylome data of these cell lines will be made publically available . This combined dataset puts these cell lines among the best characterized CRC cell lines, allowing researchers to select appropriate cell line models for their particular experiment, making optimal use of these novel cell lines as in vitro model for CRC. 21 CRC cell lines were analyzed
2016-02-29 | E-GEOD-67772 | biostudies-arrayexpress
Project description:Gene expression array utilizes the advantage of the big number of the significantly changed genes creating transcriptional profiles of known mutations. Creating gene expression profiles of the animal models with known genetic defect provides great opportunity for further investigation human diseases with unknown etiology. Motheaten mice with mutation in protein tyrosine phosphatase Ptpn6 have massive neutrophilic infiltration within the skin followed by autoinflammatory and autoimmune systemic pathology resembling similarity to neutrophilic dermatoses in human. Keywords: genetic modification We performed microarray study on motheaten mice with novel mutation (meb2) in protein tyrosine phosphatase non-receptor-6 (Ptpn6) in with 5 sick bone marrow samples and 5 wild type controls and found significant difference between these two groups.
2013-12-31 | E-GEOD-17161 | biostudies-arrayexpress
Project description:A mouse model utilizing knock in strategy to coexpress both oncogenic ErbB2 (NeuNT) and a PI3KCA mutation H1047R Microarray was used to determine gene expression change due to H1047R mutation by comparison between ErbB2 KI tumors expressing either wild type or mutant allele.
2022-03-11 | GSE198377 | GEO
Project description:We found a novel MEN1 p. R21Afs mutaion in a multiple endocrine neoplasia type 1 family. To investigate the pathogenic function of p.R21Afs MEN1 mutation, the leukocyte transcriptoma profilings derived from MEN1 patients with heterozygote p.R21Afs MEN1 mutation was compared with the unaffected relatives without p.R21Afs MEN1 mutation.
2023-02-01 | GSE221993 | GEO
Project description:Inherited or sporadic mutations in the transcription factor GATA2 have been shown to be responsible for MonoMAC syndrome, a GATA2 deficiency disease characterized by a constellation of findings including disseminated non-tuberculous mycobacterial infections, severe deficiencies of monocytes, natural killer cells, and B-lymphocytes, and myelodysplastic syndrome. Mutations in the GATA2 gene are found in ~90% of patients with a GATA2 deficiency phenotype and are largely missense mutations in the conserved second zinc-finger domain or truncation mutations elsewhere in the coding sequence. Mutations in an intron 5 regulatory enhancer element are also well described in GATA2 deficiency. Here we present a large multigeneration kindred with the clinical features of GATA2 deficiency but lacking an apparent GATA2 mutation. Whole Genome Sequencing revealed a unique Adenine-to-Thymine variant in the GATA2 -110 enhancer 116,855bp upstream of the GATA2 gene. The mutation creates a new E-box consensus in position with an existing GATA-box to generate a new hematopoietic regulatory composite element. The mutation segregates with the disease pattern in five generations of the family pedigree. Cell-type specific allelic imbalance of GATA2 expression is observed in a patient’s bone marrow with higher expression from the mutant-linked allele. Allele-specific overexpression of GATA2 is observed in CRISPR/Cas9-modified HL60 cultured cells and in luciferase assays with the enhancer mutation. This study demonstrates overexpression of GATA2 resulting from a single nucleotide change in an upstream regulatory enhancer element in patients with MonoMAC syndrome.
2023-10-31 | GSE227436 | GEO
Project description:We identified a novel germline mutation of the microphthalmia-associated transcription factor (MITF - E318K). This mutation was found to be present in numerous melanoma families, as well as the general population, where its association with melanoma has a significant effect. We determined the effect of the E318K mutation on global MITF target gene transcription. We developed a tetracycline-inducible system for expression of wild type MITF or the E318K variant in melanoma cell lines with constitutively low or undetectable levels of endogenous MITF (HT144 and C32). We examined whole-genome expression profiles in these cells following induction of either wild-type or E318K MITF for 48 hours. Analysis suggests that the MITF E318K mutant exhibits differential transcriptional activity against some, though not all, target genes.
2011-12-01 | GSE31269 | GEO
Project description:Many cancers carry recurrent change-of-function mutations in RNA splicing factor genes, which induce sequence-specific changes in RNA splicing. Here, we describe a method to harness this change in RNA splicing activity to drive splicing factor mutation-dependent gene expression in cancers and selectively eliminate these tumors. We engineered synthetic introns which were efficiently spliced in leukemia and breast epithelial cells bearing the most common SF3B1 mutations, but unspliced in wild-type cells—and vice versa—to yield mutation-dependent protein production. A massively parallel screen of 8,881 distinct introns delineated ideal intronic size, mapped essential sequence elements, and revealed the basis of mutation-dependent splicing. Synthetic introns enabled mutation-dependent expression of herpes simplex virus thymidine kinase and subsequent ganciclovir-mediated elimination of leukemia and breast epithelial cells bearing SF3B1 mutations, while leaving wild-type cells unaffected. This approach significantly decreased the growth of otherwise lethal leukemia xenografts and correspondingly improved host survival. The modular, compact, and specific nature of synthetic introns thereby provide a means to exploit cancer-specific changes in RNA splicing for genotype-dependent gene expression and gene therapy.
2021-12-30 | GSE163217 | GEO