Mutation in the DNMT3B DNA methyltransferase gene is a common cause of ICF (immunodeficiency, centromeric heterochromatin, facial anomalies) immunodeficiency syndrome and leads to hypomethylation of satellites 2 and 3 in pericentric heterochromatin.
Lsh/HELLS is critical for normal development and mutations of Lsh in human cause the ICF (Immune deficiency, Centromeric instability, Facial anomalies) syndrome, a severe immune disorder with multiple organ deficiencies.
ATM, the gene mutated in the human immunodeficiency disorder ataxia-telangiectasia (A-T), plays a central role in recognizing ionizing radiation damage in DNA and in controlling several cell cycle checkpoints.
Expression of the main human NBS allele rescues the lethality of Nbs1-/- mice, but leads to immunodeficiency, cancer predisposition, a defect in meiotic progression in females and cell-cycle checkpoint defects that are associated with a partial reduction in Atm activity.
Here we show that an N-ethyl-N-nitrosourea-induced nonsense mutation of Cd36 (oblivious) causes a recessive immunodeficiency phenotype in which macrophages are insensitive to the R-enantiomer of MALP-2 (a diacylated bacterial lipopeptide) and to lipoteichoic acid.
Notably, a conserved tryptophan residue (W453) that constitutes a key structural component of the K4me3-binding surface and is essential for RAG2's recognition of H3K4me3 is mutated in patients with immunodeficiency syndromes.
Here, we created an immunodeficient rat with a functional deletion of the Recombination Activating Gene 2 (<i>Rag2</i>) gene, using genetically modified spermatogonial stem cells (SSC).
We aimed to assess engraftment, vasculogenic and pro-angiogenic activities of ECFC in immunocompetent (C57BL/6: WT) or immunodeficient (rag1 <sup>-/-</sup> C57BL/6: Rag1) mice.
Previously, we established that facial MN (FMN) survival levels in the SOD1(G93A) transgenic mouse model of ALS are reduced and nerve regeneration is delayed, similar to immunodeficientRAG2(-/-) mice, after facial nerve axotomy.
The human ovarian carcinoma SK-OV-3 cells implanted intraperitoneally (i.p.) in immunodeficientRag2⁻/⁻;Il2rg⁻/⁻ mice gave rise to a progressive peritoneal carcinomatosis which mimics the fatal condition in advanced human patients.I.p. administration of R-LM249 strongly inhibited carcinomatosis, resulting in 60% of mice free from peritoneal diffusion, and 95% reduction in the total weight of neoplastic nodules.
The RAG1-RAG2 structure rationalizes more than 60 mutations identified in immunodeficient patients, as well as a large body of genetic and biochemical data.
X-linked hyper IgM Syndrome (XLHIGM), the most frequent form of the Hyper IgM syndromes is a primary immune deficiency resulting from a mutation in the CD40 ligand gene (CD40LG).
Telomerase reverse transcriptase promoter mutations were searched in 72 conjunctiva neoplasia cases, comprising SCC and intraepithelial neoplasia grade 1-3 (CIN1-3), as well as in 53 conjunctiva normal tissues and in 24 HIV-related Kaposi sarcoma.
These observations are consistent with previous reports that hyperactivating mutations in PIK3CD, which encodes the p110δ catalytic subunit, are capable of promoting immune deficiency.
Unlike WT, all mutants failed to suppress colony formation and some mutants skewed cell fate to granulocytes, consistent with the monocytopenia phenotype seen in GATA2-related immunodeficiency disorders.
We report a case of MonoMAC syndrome in a patient with a GATA2 mutation and discuss the manifestations, diagnosis, and treatment of this novel immunodeficiency disorder.
Germline GATA2 mutations are involved in a group of complex syndromes with overlapping clinical features of immune deficiency, lymphedema and propensity to acute myeloid leukemia or myelodysplastic syndrome (AML-MDS).
In 2012, mutations in the lipopolysaccharide-responsive beige-like anchor (LRBA) gene were identified as the cause of an autoimmunity and immunodeficiency syndrome.