Project description:Whole Exome sequencing of two patients with Cardiac angiosarcoma in Li-Fraumeni-like families discovers that a mutation in the pot1 gene is responsible for cardiac angiosarcoma in tp53-negative li-fraumeni-like families
Project description:We report the application for high-throughput profiling of transcriptome, chromatin-associated proteins and histone-modifications on a genome-wide level in iPSC-derived family control astrocytes vs LFS (Li-Fraumeni Syndrome) patient astrocytes.
Project description:The underlying change of gene network expression of Guillain-Barre syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signalling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. Quantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls.
Project description:Genome wide DNA methylation profiling of peripheral blood cells from WHS and several disease patients. The Illumina Infinium EPIC Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in peripheral blood samples. Samples included, 20 WHS, 1 patient with heterozygous deletion in 4p16.2p15.31, 2 Sotos syndrome patients, 2 Kabuki syndrome patients, 1 CHARGE syndrome patient, and 3 patients who harbor NSD2 de novo variants.
Project description:Hyper IgE Recurrent Infection Syndrome (HIES or Jobâs syndrome), is a rare disorder of immunity and connective tissue, typically manifest with boils, cyst-forming pneumonias, and extremely elevated serum IgE as well as retained primary dentition and bone abnormalities. Inheritance can be autosomal dominant. In order to identify a specific defect or gene of interest, we performed microarray expression analysis on samples from patients with Job's syndrome and from healthy control subjects. Experiment Overall Design: Polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood from patients with Job's syndrome and healthy control subjects. PMNs and PBMCs were incubated with or without IgG- and C3bi-coated latex beads for 3 and 6 hours.
Project description:Multiple family members with cancer or individuals with multiple primary cancers are indicative of potential genetic etiology1. Germline mutations in TP53 cause a rare high penetrance cancer syndrome, Li Fraumeni Syndrome (LFS)2. We identified a TP53 tetramerization domain (TD) missense mutation c.1000G>C;p.G334R, in a family with LFS-associated cancers. Twenty-one additional probands were identified, and available tumors showed biallelic somatic inactivation of TP53. The majority of families were of Ashkenazi Jewish descent, and the TP53 c.1000G>C allele was found on a commonly inherited haplotype. While classical p53 target gene activation was maintained in p.G334R mutant cell lines treated with Nutlin-3a, a subset of p53 target genes, including PCLO, PLTP, PLXNB3 and LCN15, showed defective transactivation. Structural analysis demonstrated thermal instability of the mutant TD, and the G334R mutant protein showed increased preponderance of mutant conformation protein. TP53 c.1000G>C;p.G334R is a rare AJ-predominant mutation associated with low penetrance Li-Fraumeni Syndrome
