Project description:Combined immunodeficiencies are a heterogeneous collection of primary immune disorders that exhibit defects in T cell development or function, along with impaired B cell activity even in light of normal B cell maturation. CARMIL2 (RLTPR) is a protein involved in cytoskeletal organization and cell migration which also plays a role in CD28 co-signaling of T cells. Mutations in this protein have recently been reported to cause a novel primary immunodeficiency disorder with variable phenotypic presentations. Here we deposit genotyping data for seven patients from three unrelated, consanguineous multiplex families that presented with dermatitis, eosophagitis and recurrent skin and chest infections with evidence of combined immunodeficiency. By using this genotyping data to perform autozygome-guided analysis, and coupling it with the results of whole exome sequencing, we uncovered two mutations not previously reported (p.R50T and p.L846Sfs) in CARMIL2.
Project description:This study reports two unrelated patients with a combined immunodeficiency. Whole-exome sequencing of both patients, their healthy parents and siblings identified in both families a /de novo/ missense variant in /ITPR3/ (NM_002224.3:c.7570C>T, p.Arg2524Cys). While the mRNA level in patients remained the same as in healthy siblings and controls, the level of protein expression was diminished. It was also shown that the ITPR3 heterozygous p.Arg2524Cys mutation impairs calcium flux function in dermal fibroblast of one patient and in a knock-in Jurkat T cell line.
2024-06-18 | PXD038284 | Pride
Project description:The human oropharyngeal microbiota and common variable immunodeficiency
| PRJNA744071 | ENA
Project description:Gamma/delta TCR repertoire in Common Variable Immunodeficiency
| PRJNA1055292 | ENA
Project description:The human oropharyngeal microbiota and common variable immunodeficiency
Project description:Germline heterozygous GATA2 mutations cause GATA2 deficiency, a complex disorder characterized by bone marrow failure, immunodeficiency, and a high risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The disease evolves variably among patients, leading to anxiety for families. Due to phenotypic diversity and clinical overlap, timely diagnosis is often challenging. GATA2 carriers exhibit variable expressivity, with some developing early-onset MDS while others remain asymptomatic, suggesting that genetic and epigenetic factors influence disease progression. While advances in diagnostics through whole-exome sequencing (WES) and whole genome sequencing (WGS) have been made, few epigenetic studies have focused on GATA-related MDS. We present a familial case of four GATA2 carriers, two of whom are asymptomatic and two have developed MDS. Notably, we conducted a longitudinal epigenome analysis of one patient, tracking progression from asymptomatic to MDS, providing key insights with potential clinical applications
Project description:Germline heterozygous GATA2 mutations cause GATA2 deficiency, a complex disorder characterized by bone marrow failure, immunodeficiency, and a high risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The disease evolves variably among patients, leading to anxiety for families. Due to phenotypic diversity and clinical overlap, timely diagnosis is often challenging. GATA2 carriers exhibit variable expressivity, with some developing early-onset MDS while others remain asymptomatic, suggesting that genetic and epigenetic factors influence disease progression. While advances in diagnostics through whole-exome sequencing (WES) and whole genome sequencing (WGS) have been made, few epigenetic studies have focused on GATA-related MDS. We present a familial case of four GATA2 carriers, two of whom are asymptomatic and two have developed MDS. Notably, we conducted a longitudinal epigenome analysis of one patient, tracking progression from asymptomatic to MDS, providing key insights with potential clinical applications