Multibranched chromosomes 1, 9, and 16 in a patient with combined IgA and IgE deficiency

Tiepolo, L.; Maraschio, P; Gimelli, Giorgio; Cuoco, Cristina; Gargani, G; Romano, C.

doi:10.1007/bf00287166

Cited by 110 publications

(74 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ICF syndrome patients also exhibit hypomethylation of satellite 2 repeats in the pericentromeric heterochromatin, and rearrangements of chromosomes 1, 9 and 16 via hypomethylated satellite 2 in lymphocytes to form multiradiate chromosomes (Jeanpierre et al, 1993;Xu et al, 1999). It should be noted that chromosomal rearrangements have been observed in bone marrow cells from only one of four patients studied (Fasth et al, 1990;Hulten, 1978;Smeets et al, 1994;Turleau et al, 1989), and have never been detected in fibroblast cells derived from four ICF syndrome patients (Brown et al, 1995;Carpenter et al, 1988;Maraschio et al, 1988;Tiepolo et al, 1979). Facial anomaly is another characteristic symptom afflicting individuals with ICF.…”

Section: Immune Defects In Dnmt3b Hypomorphic Mutantsmentioning

confidence: 95%

Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome

et al. 2006

View full text Add to dashboard Cite

ICF (Immunodeficiency, Centromeric instability and Facial anomalies) syndrome is a rare autosomal recessive disease caused by mutations in the DNA methyltransferase gene DNMT3B. To investigate the function of Dnmt3b in mouse development and to create animal models for ICF syndrome, we have generated three mutant alleles of Dnmt3b in mice: one carrying a deletion of the catalytic domain (null allele) and two carrying ICF-like missense mutations in the catalytic domain. The Dnmt3b null allele results in embryonic lethality from E14.5 to E16.5 with multiple tissue defects, including liver hypotrophy, ventricular septal defect and haemorrhage. By contrast, mice homozygous for the ICF mutations develop to term and some survive to adulthood. These mice show phenotypes that are reminiscent of ICF patients, including hypomethylation of repetitive sequences, low body weight, distinct cranial facial anomalies and T cell death by apoptosis. These results indicate that Dnmt3b plays an essential role at different stages of mouse development, and that ICF missense mutations cause partial loss of function. These mutant mice will be useful for further elucidation of the pathogenic and molecular mechanisms underlying ICF syndrome.

show abstract

Section: Immune Defects In Dnmt3b Hypomorphic Mutantsmentioning

confidence: 95%

Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Genomic instability in the rare autosomal recessive disease, ICF syndrome has been attributed to reduction or loss of DNA methylation (hypomethylation) in pericentromeric heterochromatin. 8,9 Except for a few documented cases, patients with ICF (Immunodeficiency, Centromeric instability and Facial anomalies) syndrome possess biallelic mutations in DNMT3B that ablate or drastically reduce its catalytic function leading to loss of CpG methylation of the satellite repeats in pericentromeric heterochromatin. 10,11 Hypomethylation of these repeats results in chromatin decondensation and enhanced chromosomal rearrangement leading to chromosomal arm deletions and/or formation of multiradiate chromosomes.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Dnmt3b:Thymine-DNA Glycosylase Interaction and Stimulation of Thymine Glycosylase-Mediated Repair by DNA Methyltransferase(s) and RNA

Boland

Christman

2008

Journal of Molecular Biology

View full text Add to dashboard Cite

SummaryMethylation of cytosine residues in CpG dinucleotides plays an important role in epigenetic regulation of gene expression and chromatin structure/stability in higher eukaryotes. DNA methylation patterns are established and maintained at CpG dinucleotides by DNA methyltransferases (Dnmt1 and Dnmts 3a and 3b). In mammals and many other eukaryotes, the CpG dinucleotide is underrepresented in the genome. This loss is postulated to be the result of unrepaired deamination of cytosine (C) and 5-methylcytosine (5mC) to uracil (U) and thymine (T), respectively. Two thymine glycosylases are believed to reduce the impact of 5mC deamination. G/T mismatchspecific thymine-DNA glycosylase (Tdg) and methyl-CpG binding domain protein 4 (Mbd4) can both excise uracil or thymine at U·G and T·G mismatches to initiate base excision repair. Here, we report the characterization of interactions between Dnmt3b and both Tdg and Mbd4. Our results demonstrate that both Tdg and Dnmt3b are colocalized to heterochromatin and also demonstrate reduction of T·G mismatch repair efficiency upon loss of DNA methyltransferase expression as well as a requirement for an RNA component for correct T·G mismatch repair.

show abstract

“…Cytogenetic abnormalities include elongation of centromeric or juxtacentromeric heterochromatin of chromosomes 1, 9, and 16, leading to formation of multiradiate figures involving mainly chromosomes 1 and 16. 17 ICF patients show marked hypomethylation of classical satellites II and III, leading to centromeric instability. 18,19 Most ICF patients (around 65%) [20][21][22] carry mutations in the catalytic domain of the DNA methyltransferase 3B (DNMT3B) gene.…”

Section: Introductionmentioning

confidence: 99%

Defective B-cell-negative selection and terminal differentiation in the ICF syndrome

Blanco-Betancourt

Moncla

Milili

et al. 2004

Blood

View full text Add to dashboard Cite

IntroductionIn the bone marrow (BM), B-cell differentiation leads to generation of a broad repertoire of antibody-bearing cells in an antigenindependent manner. After ordered rearrangement of the heavy and light chain loci, immature B cells are the first B-cell subset to express a B-cell receptor (BCR), composed of a surface immunoglobulin M (IgM) and the Ig␣/Ig␤ signaling complex (reviewed in Meffre et al 1 ). This process yields a number of potentially self-reactive clones, which can be eliminated by apoptosis (clonal deletion), modified by secondary rearrangements (receptor editing), or rendered hyporesponsive (anergy). [2][3][4][5] In the mouse, 2 ϫ 10 7 immature B cells are generated every day, of which around 90% undergo negative selection. 6 Before migrating to the periphery, immature B cells develop into IgM hi IgD lo CD21 Ϫ CD23 Ϫ type 1 (T1) transitional B cells. 7 They differentiate in the spleen into IgM hi IgD ϩ CD21 ϩ CD23 ϩ type 2 (T2) transitional B cells and then into either IgM hi IgD Ϫ CD21 ϩ CD23 Ϫ marginal zone or IgM lo IgD hi CD21 ϩ CD23 ϩ follicular mature B cells. 8 Both transitional B-cell subsets appear to be short lived (3 to 4 days) 6 and nondividing in vivo, 9 although recent studies show that T2's proliferate and up-regulate survival signals, whereas T1's die after in vitro BCR engagement. 10 Moreover, T1's express CD95 but not the antiapoptotic molecule bcl-2, 7 further suggesting that T1 might be the target of the B-cell-negative selection occurring in the periphery. 11 Such transitional B-cell subsets have not yet been defined in humans. Current characterization of human peripheral blood (PB) B cells is based on the expression of the tumor necrosis factor family member CD27, which distinguishes unmutated IgM ϩ IgD ϩ CD27 Ϫ naive cells (approximately 60% in adults) from somatically hypermutated CD27 ϩ memory cells (40%, of which approximately 40% are IgM ϩ IgD ϩ ). 12 Naive B cells may be the target of negative selection, since heavy chain variable region (V H ) usage as well as the V H complementarity determining region 3 (CDR3) length changes in peripheral mature B cells. [13][14][15] The analysis of primary immune deficiencies is a powerful tool for the study of normal human B-cell differentiation. Immunodeficiency, centromeric region instability, and facial anomalies (ICF) disease is a rare autosomal recessive syndrome, characterized by chromosomal instability and humoral immune deficiency. Patients present recurrent respiratory infections and diarrhea as consequence of hypogammaglobulinemia or agammaglobulinemia, sometimes associated with defective cell-mediated immunity. 16 Developmental defects such as delayed developmental milestones, facial dismorphy (eg, roundness, hypertelorism, macroglossia), and mental retardation have also been observed. Cytogenetic abnormalities include elongation of centromeric or juxtacentromeric heterochromatin of chromosomes 1, 9, and 16, leading to formation of multiradiate figures involving mainly chromosomes 1 and 16. 17 ICF patients show ma...

show abstract

Multibranched chromosomes 1, 9, and 16 in a patient with combined IgA and IgE deficiency

Cited by 110 publications

References 9 publications

Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome

Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome

Characterization of Dnmt3b:Thymine-DNA Glycosylase Interaction and Stimulation of Thymine Glycosylase-Mediated Repair by DNA Methyltransferase(s) and RNA

Defective B-cell-negative selection and terminal differentiation in the ICF syndrome

Contact Info

Product

Resources

About