ICF
MCID: IMM011
MIFTS: 43

Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome (ICF)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Immunodeficiency-Centromeric Instability-Facial Anomalies...

MalaCards integrated aliases for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

Name: Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 12 53 59 15 40
Icf Syndrome 12 76 53 59 55
Immunodeficiency Syndrome, Variable 53 73
Icf 76 3
Immune Deficiency, Variable, with Centromeric Instability of Chromosomes 1, 9, and 16 53
Centromeric Instability, Immunodeficiency Syndrome 53
Ciid 53

Characteristics:

Orphanet epidemiological data:

59
icf syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

Classifications:

Orphanet: 59  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0090007
ICD10 33 D84.8
Orphanet 59 ORPHA2268
ICD10 via Orphanet 34 D84.8
UMLS 73 C0398788

Summaries for Immunodeficiency-Centromeric Instability-Facial Anomalies...

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2268Disease definitionThe Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9.EpidemiologyICF has been described in about 50 patients worldwide.Clinical descriptionOther variable symptoms of this probably under-diagnosed syndrome include mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation. Serum levels of IgG, IgM, IgE, and/or IgA are low, although the type of immunoglobulin deficiency is variable. Recurrent infections are the presenting symptom, usually in early childhood.EtiologyICF always involves limited hypomethylation of DNA and often arises from mutations in one of the DNA methyltransferase genes (DNMT3B). Much of this DNA hypomethylation is in the 1qh, 9qh, and 16qh, regions that are the site of whole-arm deletions, chromatid and chromosome breaks, stretching (decondensation), and multiradial chromosome junctions in mitogen-stimulated lymphocytes. By an unknown mechanism, the DNMT3B deficiency that causes ICF interferes with lymphogenesis (at a step after class switching) or lymphocyte activation.Antenatal diagnosisWith the identification of DNMT3B as the affected gene in a majority of ICF patients, prenatal diagnosis of ICF is possible. However, given the variety of DNMT3B mutations, a first-degree affected relative should first have both alleles of this gene sequenced.Management and treatmentTreatment almost always includes regular infusions of immunoglobulins, mostly intravenously. Recently, bone marrow transplantation has been tried.Visit the Orphanet disease page for more resources.

MalaCards based summary : Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome, also known as icf syndrome, is related to immunodeficiency-centromeric instability-facial anomalies syndrome 2 and immunodeficiency-centromeric instability-facial anomalies syndrome 1, and has symptoms including diarrhea An important gene associated with Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome is ZBTB24 (Zinc Finger And BTB Domain Containing 24), and among its related pathways/superpathways are Chromatin Regulation / Acetylation and Sulfur amino acid metabolism. Affiliated tissues include bone, b cells and bone marrow, and related phenotypes are macrocephaly and hypertelorism

Disease Ontology : 12 An autosomal recessive disease characterized by immunodeficiency, rearrangements in the vicinity of the centromeres of chromosomes 1, 9, and 16 and facial anomalies in most cases.

CDC : 3 After ten years of international revision efforts coordinated by the World Health Organization (WHO), the World Health Assembly on May 22, 2001, approved the International Classification of Functioning, Disability and Health and its abbreviation of "ICF." This classification was first created in 1980 (and then called the International Classification of Impairments, Disabilities, and Handicaps, or ICIDH) by WHO to provide a unifying framework for classifying the consequences of disease.

Wikipedia : 76 Jean Baptiste Point du Sable (before 1750 ? 1818) is honored as the first permanent non-Native-American... more...

Related Diseases for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Diseases related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 68)
# Related Disease Score Top Affiliating Genes
1 immunodeficiency-centromeric instability-facial anomalies syndrome 2 34.8 LOC105377935 MICAL1 ZBTB24
2 immunodeficiency-centromeric instability-facial anomalies syndrome 1 34.4 DNMT1 DNMT3B VAMP7
3 immunodeficiency-centromeric instability-facial anomalies syndrome 3 13.0
4 immunodeficiency-centromeric instability-facial anomalies syndrome 4 13.0
5 coffin-lowry syndrome 11.1
6 immunodeficiency, centromere instability and facial anomalies syndrome 11.1
7 combined t cell and b cell immunodeficiency 10.3
8 cerebral palsy 10.1
9 lymphedema 10.1
10 spinal cord injury 10.1
11 neuromuscular disease 10.1
12 autism 10.0
13 taylor's syndrome 10.0 DNMT1 DNMT3L
14 testicular spermatocytic seminoma 10.0 DNMT3A DNMT3B DNMT3L
15 mutagen sensitivity 10.0 DNMT1 DNMT3B
16 rheumatoid arthritis 9.9
17 neural tube defects 9.9
18 global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies 9.9
19 arthritis 9.9
20 autism spectrum disorder 9.9
21 aphasia 9.9
22 quadriplegia 9.9
23 developmental coordination disorder 9.9
24 developmental dyspraxia 9.9
25 testis seminoma 9.9 DNMT3A DNMT3B DNMT3L
26 kabuki syndrome 1 9.8 DNMT3B LOC105377935 XIST ZBTB24
27 lymphoma, hodgkin, classic 9.8
28 immunodysregulation, polyendocrinopathy, and enteropathy, x-linked 9.8
29 rett syndrome 9.8
30 leukemia 9.8
31 angiosarcoma 9.8
32 agammaglobulinemia 9.8
33 progressive multifocal leukoencephalopathy 9.8
34 rubella 9.8
35 acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) 9.8
36 achondroplasia 9.8
37 spondyloarthropathy 1 9.8
38 gilles de la tourette syndrome 9.8
39 attention deficit-hyperactivity disorder 9.8
40 schizophrenia 9.8
41 cystic fibrosis 9.8
42 myasthenia gravis 9.8
43 retinitis pigmentosa 9.8
44 usher syndrome, type i 9.8
45 retinitis pigmentosa-deafness syndrome 9.8
46 leber congenital amaurosis 4 9.8
47 ischemic heart disease 9.8
48 morbid obesity 9.8
49 asperger syndrome 9.8
50 usher syndrome 9.8

Graphical network of the top 20 diseases related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:



Diseases related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome

Symptoms & Phenotypes for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Human phenotypes related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

59 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 Frequent (79-30%)
2 hypertelorism 59 Occasional (29-5%)
3 low-set ears 59 Occasional (29-5%)
4 intellectual disability 59 Frequent (79-30%)
5 macroglossia 59 Occasional (29-5%)
6 global developmental delay 59 Frequent (79-30%)
7 recurrent respiratory infections 59 Very frequent (99-80%)
8 depressed nasal bridge 59 Frequent (79-30%)
9 umbilical hernia 59 Occasional (29-5%)
10 malabsorption 59 Frequent (79-30%)
11 short stature 59 Very frequent (99-80%)
12 immunodeficiency 59 Very frequent (99-80%)
13 anemia 59 Frequent (79-30%)
14 micrognathia 59 Very frequent (99-80%)
15 epicanthus 59 Occasional (29-5%)
16 flat face 59 Occasional (29-5%)
17 decreased antibody level in blood 59 Very frequent (99-80%)
18 lymphopenia 59 Frequent (79-30%)
19 abnormality of chromosome stability 59 Very frequent (99-80%)
20 cellular immunodeficiency 59 Frequent (79-30%)
21 protruding tongue 59 Occasional (29-5%)
22 abnormality of neutrophils 59 Frequent (79-30%)
23 communicating hydrocephalus 59 Frequent (79-30%)

UMLS symptoms related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:


diarrhea

Drugs & Therapeutics for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Search Clinical Trials , NIH Clinical Center for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome

Genetic Tests for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Anatomical Context for Immunodeficiency-Centromeric Instability-Facial Anomalies...

MalaCards organs/tissues related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

41
Bone, B Cells, Bone Marrow, Heart, Spinal Cord, Testis, Myeloid

Publications for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Articles related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

(show all 45)
# Title Authors Year
1
HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome. ( 29339483 )
2018
2
Clinical and Immunological Characterization of ICF Syndrome in Japan. ( 30353301 )
2018
3
Pericentromeric hypomethylation elicits an interferon response in an animal model of ICF syndrome. ( 30484769 )
2018
4
Three Types of Immunodeficiency, Centromeric Instability, and Facial Anomalies (ICF) Syndrome Identified by Whole-Exome Sequencing in Saudi Hypogammaglobulinemia Patients: Clinical, Molecular, and Cytogenetic Features. ( 30511102 )
2018
5
Telomeres in ICF syndrome cells are vulnerable to DNA damage due to elevated DNA:RNA hybrids. ( 28117327 )
2017
6
Corrigendum: Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome. ( 27328760 )
2016
7
Genetic, Cellular and Clinical Features of ICF Syndrome: a French National Survey. ( 26851945 )
2016
8
Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome. ( 26216346 )
2015
9
Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome. ( 26161907 )
2015
10
Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2). ( 25330735 )
2014
11
Dnmt3b Prefers Germ Line Genes and Centromeric Regions: Lessons from the ICF Syndrome and Cancer and Implications for Diseases. ( 25198254 )
2014
12
Characterization and rescue of telomeric abnormalities in ICF syndrome type I fibroblasts. ( 23450006 )
2013
13
Immunodeficiency, centromeric region instability and facial anomalies (ICF) syndrome diagnosed in an adult who is now a long-term survivor. ( 23917367 )
2013
14
Generation of an ICF syndrome model by efficient genome editing of human induced pluripotent stem cells using the CRISPR system. ( 24084724 )
2013
15
3D position of pericentromeric heterochromatin within the nucleus of a patient with ICF syndrome. ( 21554265 )
2012
16
Lymphoid tissue histology in a patient with ICF syndrome. ( 22697015 )
2012
17
Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome, due to ZBTB24 mutations, presenting with large cerebral cyst. ( 22786748 )
2012
18
TERRA, CpG methylation and telomere heterochromatin: lessons from ICF syndrome cells. ( 20016274 )
2010
19
Altered intra-nuclear organisation of heterochromatin and genes in ICF syndrome. ( 20613881 )
2010
20
Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). ( 17893117 )
2008
21
ICF syndrome: high variability of the chromosomal phenotype and association with classical Hodgkin lymphoma. ( 17702009 )
2007
22
Interphase chromosomal abnormalities and mitotic missegregation of hypomethylated sequences in ICF syndrome cells. ( 15856360 )
2005
23
A case with ICF syndrome lost to rubella pneumonitis. ( 15884637 )
2005
24
A novel case of immunodeficiency, centromeric instability, and facial anomalies (the ICF syndrome): immunologic and cytogenetic studies. ( 11869951 )
2002
25
ICF syndrome cells as a model system for studying X chromosome inactivation. ( 12900541 )
2002
26
T-cell apoptosis in ICF syndrome. ( 11496256 )
2001
27
Satellite 2 methylation patterns in normal and ICF syndrome cells and association of hypomethylation with advanced replication. ( 11702227 )
2001
28
High frequencies of ICF syndrome-like pericentromeric heterochromatin decondensation and breakage in chromosome 1 in a chorionic villus sample. ( 11768395 )
2001
29
The ICF syndrome: new case and update. ( 11837609 )
2001
30
DNA hypomethylation and unusual chromosome instability in cell lines from ICF syndrome patients. ( 10894953 )
2000
31
Early prenatal diagnosis of the ICF syndrome. ( 11038463 )
2000
32
Escape from gene silencing in ICF syndrome: evidence for advanced replication time as a major determinant. ( 11063717 )
2000
33
Localization of the ICF syndrome to chromosome 20 by homozygosity mapping. ( 9718351 )
1998
34
A FISH study of chromosome fusion in the ICF syndrome: involvement of paracentric heterochromatin but not of the centromeres themselves. ( 9783707 )
1998
35
Undermethylation of Alu sequences in ICF syndrome: molecular and in situ analysis. ( 9284945 )
1997
36
Variability of clinical and immunological phenotype in immunodeficiency-centromeric instability-facial anomalies syndrome. Report of two new patients and review of the literature. ( 8529685 )
1995
37
ICF syndrome (immunodeficiency, centromeric instability and facial anomalies): investigation of heterochromatin abnormalities and review of clinical outcome. ( 7557962 )
1995
38
Chromosome instability in ICF syndrome: formation of micronuclei from multibranched chromosomes 1 demonstrated by fluorescence in situ hybridization. ( 7625446 )
1995
39
ICF syndrome: a new case and review of the literature. ( 8076938 )
1994
40
An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome. ( 8102570 )
1993
41
Interphase cytogenetics of the ICF syndrome. ( 1449239 )
1992
42
Multibranched chromosomes in the ICF syndrome: immunodeficiency, centromeric instability, and facial anomalies. ( 2729362 )
1989
43
Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome. ( 3351904 )
1988
44
Symposium on the diagnosis and treatment of intravascular coagulation-fibrinolysis (ICF) syndrome, with special emphasis on this syndrome in patients with cancer. Introduction. ( 4416013 )
1974
45
Intravascular coagulation-fibrinolysis (ICF) syndrome. ( 4263611 )
1972

Variations for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Expression for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Search GEO for disease gene expression data for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome.

Pathways for Immunodeficiency-Centromeric Instability-Facial Anomalies...

GO Terms for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Cellular components related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 pericentric heterochromatin GO:0005721 9.16 DNMT1 HELLS
2 XY body GO:0001741 8.96 DNMT3A SUMO1
3 heterochromatin GO:0000792 8.8 DNMT1 DNMT3A SUMO1

Biological processes related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.93 DNMT1 DNMT3A DNMT3B SUMO1 ZBTB24
2 regulation of gene expression GO:0010468 9.74 DNMT1 DNMT3A DNMT3B
3 methylation GO:0032259 9.72 DNMT1 DNMT3A DNMT3B
4 response to ionizing radiation GO:0010212 9.58 DNMT3A DNMT3B
5 response to cocaine GO:0042220 9.56 DNMT3A DNMT3B
6 DNA methylation involved in gamete generation GO:0043046 9.52 DNMT3A DNMT3L
7 response to vitamin A GO:0033189 9.51 DNMT3A DNMT3B
8 positive regulation of histone H3-K4 methylation GO:0051571 9.49 DNMT1 DNMT3B
9 regulation of gene expression by genetic imprinting GO:0006349 9.48 DNMT3A DNMT3L
10 methylation-dependent chromatin silencing GO:0006346 9.46 DNMT3A HELLS
11 gene silencing GO:0016458 9.43 DNMT1 XIST
12 negative regulation of gene expression, epigenetic GO:0045814 9.43 DNMT1 DNMT3A DNMT3B
13 maintenance of DNA methylation GO:0010216 9.4 DNMT1 HELLS
14 DNA methylation involved in embryo development GO:0043045 9.37 DNMT1 DNMT3A
15 C-5 methylation of cytosine GO:0090116 9.33 DNMT1 DNMT3A DNMT3B
16 negative regulation of histone H3-K9 methylation GO:0051573 9.32 DNMT1 DNMT3B
17 DNA methylation on cytosine GO:0032776 9.13 DNMT1 DNMT3A DNMT3L
18 DNA methylation GO:0006306 9.02 DNMT1 DNMT3A DNMT3B DNMT3L HELLS

Molecular functions related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin binding GO:0003682 9.46 DNMT1 DNMT3A DNMT3B HELLS
2 methyltransferase activity GO:0008168 9.43 DNMT1 DNMT3A DNMT3B
3 DNA-methyltransferase activity GO:0009008 9.13 DNMT1 DNMT3A DNMT3B
4 DNA (cytosine-5-)-methyltransferase activity GO:0003886 8.8 DNMT1 DNMT3A DNMT3B

Sources for Immunodeficiency-Centromeric Instability-Facial Anomalies...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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