variable Immunodeficiency syndrome

A rare autosomal recessive disorder characterized by facial abnormalities, immunoglobulin deficiency, and branching of chromosomes 1, 9, and 16 after PHYTOHEMAGGLUTININ stimulation of LYMPHOCYTES. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients that is explained by mutations in the DNMT3B gene in some, but not all,cases. OMIM: 242860

Also Known As:

Networked: 94 relevant articles (1 outcomes, 5 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Agammaglobulinemia (Hypogammaglobulinemia)
2.	Chromosome Aberrations (Chromosome Abnormalities)
3.	Genomic Instability
4.	Inborn Genetic Diseases (Disease, Hereditary)
5.	Neoplasms (Cancer)

Experts

1.	Sasaki, Hiroyuki: 7 articles (11/2019 - 09/2004)
2.	Ehrlich, M: 6 articles (04/2006 - 01/2000)
3.	Francastel, Claire: 5 articles (01/2019 - 07/2013)
4.	Velasco, Guillaume: 5 articles (01/2019 - 07/2013)
5.	Robertson, Keith D: 5 articles (11/2018 - 09/2002)
6.	Tsien, F: 4 articles (01/2002 - 01/2000)
7.	Unoki, Motoko: 3 articles (11/2019 - 07/2013)
8.	van der Maarel, Silvère M: 3 articles (01/2019 - 06/2011)
9.	Kubota, Takeo: 3 articles (11/2018 - 09/2004)
10.	Sagie, Shira: 3 articles (11/2017 - 07/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to variable Immunodeficiency syndrome:

1.	Immunoglobulins (Immunoglobulin)IBA 04/17/2014 - "Early diagnosis of ICF syndrome is crucial since early immunoglobulin supplementation can improve the course of disease. " 02/01/2008 - "Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. " 12/01/2000 - "ICF syndrome is a rare autosomal recessive immunoglobulin deficiency, sometimes combined with defective cellular immunity. " 02/01/1994 - "[Reconstitution of immunoglobulin production in patients with variable immunodeficiency syndrome (CVI) by the CD40 system and IL-10]." 04/01/1993 - "[In vitro IL-6- and immunoglobulin-production in patients with variable immunodeficiency syndrome (CVID)]."
2.	DNA (Deoxyribonucleic Acid)IBA 12/01/2023 - "Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency. " 03/11/2023 - "Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency. " 07/01/2013 - "Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that shows DNA hypomethylation at pericentromeric satellite-2 and -3 repeats in chromosomes 1, 9 and 16. " 09/01/2004 - "A 3-year-old girl with phenotypic and cytogenetic manifestations of the ICF syndrome and DNA hypomethylation but without DNMT3B gene mutation is described. " 09/01/2004 - "ICF syndrome in a girl with DNA hypomethylation but without detectable DNMT3B mutation."
3.	HeterochromatinIBA 10/01/1998 - "A FISH study of chromosome fusion in the ICF syndrome: involvement of paracentric heterochromatin but not of the centromeres themselves." 08/01/2012 - "3D position of pericentromeric heterochromatin within the nucleus of a patient with ICF syndrome." 04/29/2011 - "Immunodeficiency, Centromeric Instability, Facial Anomalies (ICF) syndrome is a rare autosomal recessive disorder that is characterized by a marked immunodeficiency, severe hypomethylation of the classical satellites 2 and 3 associated with disruption of constitutive heterochromatin, and facial anomalies. " 06/29/2010 - "Altered intra-nuclear organisation of heterochromatin and genes in ICF syndrome." 01/01/2010 - "TERRA, CpG methylation and telomere heterochromatin: lessons from ICF syndrome cells."
4.	Proteins (Proteins, Gene)FDA Link 01/01/2017 - "Mutations of the chromatin remodeling protein Lsh/HELLS can cause the human Immunodeficiency, Centromere instability and Facial anomalies (ICF) syndrome, which is associated with neurologic deficiencies. " 05/01/2006 - "Our findings suggest that methylation defects in ICF syndrome may also result from impaired stimulation of DNMT3B activity by DNMT3L or other unknown regulatory factors as well as from a weakened basal catalytic activity of the mutant DNMT3B protein per se." 01/01/2005 - "This is the first description of altered nuclear distribution of HP1 proteins in the constitutional ICF syndrome. " 01/01/2005 - "Subcellular distribution of HP1 proteins is altered in ICF syndrome." 01/01/2018 - "Together, our study identifies a unique bipartite nucleosome remodeling complex where the functional remodeling activity is split between two proteins and thus delineates the defective pathway in ICF syndrome."
5.	DNA Methyltransferase 3BIBA 02/15/2011 - "This specific hypermethylation of the active gene bodies is severely disrupted in cells of an immunodeficiency, centromeric region instability, facial anomalies (ICF) syndrome patient bearing mutated DNA methyltransferase 3B (DNMT3B). " 11/01/2008 - "Mutations of the DNA methyltransferase 3B (DNMT3B) gene have been detected in patients with immunodeficiency, centromere instability, and facial anomalies (ICF) syndrome. " 11/01/2008 - "DNA methyltransferase 3B mutant in ICF syndrome interacts non-covalently with SUMO-1." 03/01/2008 - "DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function." 12/01/2001 - "DNA methyltransferase 3B mutations linked to the ICF syndrome cause dysregulation of lymphogenesis genes."
6.	Trans-Activators (Trans-Acting Factor)IBA 11/01/1995 - "DNA, FISH and complementation studies in ICF syndrome: DNA hypomethylation of repetitive and single copy loci and evidence for a trans acting factor."
7.	Biomarkers (Surrogate Marker)IBA 04/17/2014 - "The specific and robust biomarkers identified in this study could be introduced into routine clinical immunology or neurology departments to facilitate testing of patients with suspected ICF syndrome. "
8.	Nucleosomes (Nucleosome)IBA 01/01/2018 - "HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome." 01/01/2018 - "Together, our study identifies a unique bipartite nucleosome remodeling complex where the functional remodeling activity is split between two proteins and thus delineates the defective pathway in ICF syndrome."
9.	MethyltransferasesIBA 12/01/2002 - "Mutations in the gene encoding for a de novo methyltransferase, DNMT3B, lead to an autosomal recessive Immunodeficiency, Centromeric instability and Facial anomalies (ICF) syndrome. " 01/01/2023 - "Bi-allelic hypomorphic mutations in DNMT3B disrupt DNA methyltransferase activity and lead to immunodeficiency, centromeric instability, facial anomalies syndrome, type 1 (ICF1). " 01/01/2023 - "Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is in most cases caused by mutations in either DNA methyltransferase (DNMT)3B, zinc finger and BTB domain containing 24, cell division cycle associated 7 or helicase lymphoid-specific. " 11/02/2018 - "ZBTB24, a poorly characterized zinc-finger protein, or the de novo methyltransferase DNMT3B, when mutated, cause Immunodeficiency, Centromere Instability, and Facial anomalies (ICF) syndrome, suggesting an underlying mechanistic link. " 11/01/2017 - "Mutations in the de novo DNA methyltransferase DNMT3B lead to Immunodeficiency, Centromeric Instability and Facial anomalies (ICF) syndrome, type I. This syndrome is characterized, among other hypomethylated genomic loci, by severe subtelomeric hypomethylation that is associated with abnormally short telomere length. "
10.	ChromatinIBA 01/01/2016 - "The Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome is a chromatin disorder characterized by mutations in DNMT3B, ZBTB24, CDCA7 or HELLS Here, we generated a Zbtb24 BTB domain deletion mouse and found that loss of functional Zbtb24 leads to early embryonic lethality. " 01/01/2002 - "Prolonged culture of normal chorionic villus cells yields ICF syndrome-like chromatin decondensation and rearrangements." 01/01/1999 - "Our results suggest that the genetic alteration of DNA methylation in ICF syndrome has little consequence on X chromosome gene expression and chromatin organization." 01/01/2009 - "Lessons from two human chromatin diseases, ICF syndrome and Rett syndrome." 10/15/2003 - "Here we discuss recent progress in understanding the molecular mechanisms that underlie three human genetic diseases linked to perturbations of chromatin structure: ICF syndrome, facioscapulohumeral muscular dystrophy and a case of alpha-thalassaemia."

Therapies and Procedures

1.	Therapeutics 11/01/2018 - "Hypogammaglobulinemia is a major manifestation of ICF syndrome, but immunoglobulin replacement therapy does not seem to be effective for some ICF patients. "
2.	Stem Cell Transplantation 01/01/2020 - "Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome with NK dysfunction and EBV-driven malignancy treated with stem cell transplantation."
3.	Hematopoietic Stem Cell Transplantation 01/01/2021 - "Immune Reconstitution after Hematopoietic Stem Cell Transplantation in Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome Type 1."