ICF2
MCID: IMM056
MIFTS: 34

Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2 (ICF2)

Categories: Genetic diseases, Immune diseases, Mental diseases, Neuronal diseases, Rare diseases

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

MalaCards integrated aliases for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2:

Name: Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2 56 12 73 29 6 15 71
Icf2 56 73
Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome, Type 2 39
Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome-2 13
Icf Syndrome 2 12

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
death in childhood may occur due to infection


HPO:

31
immunodeficiency-centromeric instability-facial anomalies syndrome 2:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



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

OMIM : 56 Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disorder characterized by facial dysmorphism, immunoglobulin deficiency resulting in recurrent infections, and mental retardation. Laboratory studies of patient cells show hypomethylation of satellite regions of chromosomes 1, 9, and 16, as well as pericentromeric chromosomal instability in response to phytohemagglutinin stimulation (summary by de Greef et al., 2011). For a discussion of genetic heterogeneity of immunodeficiency-centromeric instability-facial anomalies syndrome, see ICF1 (242860). (614069)

MalaCards based summary : Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2, also known as icf2, is related to immunodeficiency-centromeric instability-facial anomalies syndrome and immune deficiency disease. An important gene associated with Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2 is ZBTB24 (Zinc Finger And BTB Domain Containing 24). Affiliated tissues include b cells and t cells, and related phenotypes are hypertelorism and low-set ears

Disease Ontology : 12 An immunodeficiency-centromeric instability-facial anomalies syndrome characterized by autosomal recessive inheritance, facial dysmorphism, immunoglobulin deficiency resulting in recurrent infections, and mental retardation that has material basis in homozygous or compound heterozygous mutation in the ZBTB24 gene on chromosome 6q21.

UniProtKB/Swiss-Prot : 73 Immunodeficiency-centromeric instability-facial anomalies syndrome 2: A rare disorder characterized by a variable immunodeficiency resulting in recurrent infections, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients.

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

Graphical network of the top 20 diseases related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2:



Diseases related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2

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

Human phenotypes related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 31 HP:0000316
2 low-set ears 31 HP:0000369
3 intellectual disability 31 HP:0001249
4 high palate 31 HP:0000218
5 depressed nasal bridge 31 HP:0005280
6 short nose 31 HP:0003196
7 anteverted nares 31 HP:0000463
8 immunodeficiency 31 HP:0002721
9 retrognathia 31 HP:0000278
10 epicanthus 31 HP:0000286
11 growth delay 31 HP:0001510
12 decreased antibody level in blood 31 HP:0004313
13 motor delay 31 HP:0001270
14 short chin 31 HP:0000331
15 round face 31 HP:0000311
16 recurrent infections 31 HP:0002719
17 pneumonia 31 HP:0002090
18 chronic bronchitis 31 HP:0004469

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
epicanthal folds

Head And Neck Face:
retrognathia
round face
small chin

Respiratory Lung:
pneumonia

Neurologic Central Nervous System:
delayed motor development
mental retardation

Head And Neck Mouth:
high-arched palate

Abdomen Gastrointestinal:
gastroenteritis

Head And Neck Ears:
low-set ears

Immunology:
recurrent infections
hypogammaglobulinemia
opportunistic infections
normal numbers of absolute b cells
reduced number of memory b cells

Respiratory Airways:
chronic bronchitis

Head And Neck Nose:
small nose
flat nasal bridge
upturned nose

Growth Other:
poor growth

Laboratory Abnormalities:
hypomethylation of alpha-satellite repeats on chromosome 9
hypomethylation of satellite repeats on chromosome 1, 9, and 16
chromosomal breakage and abnormalities of the juxtacentromeric regions of chromosomes 1, 9, and 16

Clinical features from OMIM:

614069

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

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Relative Bioavailability of Batch 1 and Batch 2 of the Intended Commercial Formulation of BI 425809 Compared to Each Other and to TF 2 Formulation of BI 425809 Following Oral Administration in Healthy Male and Female Subjects (Randomized, Open-label, Single-dose, Three-treatment, Three-period, Six-sequence Crossover Study) Completed NCT03817476 Phase 1 BI 425809 (Treatment T1);BI 425809 (Treatment T2);BI 425809 (Treatment R)

Search NIH Clinical Center for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2

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

Genetic tests related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2:

# Genetic test Affiliating Genes
1 Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2 29 ZBTB24

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

MalaCards organs/tissues related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2:

40
B Cells, T Cells

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

Articles related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2:

(show all 23)
# Title Authors PMID Year
1
A novel deletion in ZBTB24 in a Lebanese family with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. 61 56 6
21906047 2012
2
Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. 61 56 6
21596365 2011
3
Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects. 61 56
23486536 2013
4
Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). 56
17893117 2008
5
The gene mutations and subtelomeric DNA methylation in immunodeficiency, centromeric instability and facial anomalies syndrome. 61
31476899 2019
6
A functional assay to classify ZBTB24 missense variants of unknown significance. 61
31066130 2019
7
ZBTB24 regulates the apoptosis of human T cells via CDCA7/TRAIL-receptor axis. 61
31030944 2019
8
Progressive Immunodeficiency with Gradual Depletion of B and CD4⁺ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2). 61
30987377 2019
9
EBV-Related Hodgkin Lymphoma in an ICF2 Patient: Is EBV Susceptibility a Hallmark of This ICF Subtype? 61
30719684 2019
10
Complete photodissociation dynamics of CF2I2 in solution. 61
30882121 2019
11
Clinical and Immunological Characterization of ICF Syndrome in Japan. 61
30353301 2018
12
Subtelomeric methylation distinguishes between subtypes of Immunodeficiency, Centromeric instability and Facial anomalies syndrome. 61
30010917 2018
13
Comparative methylome analysis of ICF patients identifies heterochromatin loci that require ZBTB24, CDCA7 and HELLS for their methylated state. 61
29659838 2018
14
Marker-assisted pyramiding of two major, broad-spectrum bacterial blight resistance genes, Xa21 and Xa33 into an elite maintainer line of rice, DRR17B. 61
30359375 2018
15
Estimation of inbreeding depression on female fertility in the Finnish Ayrshire population. 61
28748554 2017
16
Expanding the mutation spectrum in ICF syndrome: Evidence for a gender bias in ICF2. 61
28128455 2017
17
Hematopoietic Stem Cell Transplantation in a Patient With ICF2 Syndrome Presenting With EBV-Induced Hemophagocytic Lymphohystiocytosis. 61
27326813 2016
18
Downregulation of ZBTB24 hampers the G0/1- to S-phase cell-cycle transition via upregulating the expression of IRF-4 in human B cells. 61
27098601 2016
19
Genetic, Cellular and Clinical Features of ICF Syndrome: a French National Survey. 61
26851945 2016
20
Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2). 61
25330735 2014
21
Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients. 61
23739126 2013
22
Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome, due to ZBTB24 mutations, presenting with large cerebral cyst. 61
22786748 2012
23
Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma. 61
9158004 1997

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

ClinVar genetic disease variations for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ZBTB24 NM_014797.2(ZBTB24):c.958C>T (p.Arg320Ter)SNV Pathogenic 31093 rs387907104 6:109798128-109798128 6:109476925-109476925
2 ZBTB24 NM_014797.2(ZBTB24):c.833C>G (p.Ser278Ter)SNV Pathogenic 31095 6:109802397-109802397 6:109481194-109481194
3 ZBTB24 NM_014797.2(ZBTB24):c.1222T>G (p.Cys408Gly)SNV Pathogenic 31096 rs387907105 6:109796668-109796668 6:109475465-109475465
4 ZBTB24 NM_014797.2(ZBTB24):c.1369C>T (p.Arg457Ter)SNV Pathogenic 31097 rs387907106 6:109788857-109788857 6:109467654-109467654
5 ZBTB24 NM_014797.2(ZBTB24):c.396_397del (p.His132fs)deletion Pathogenic 40181 6:109802833-109802834 6:109481630-109481631
6 ZBTB24 NM_014797.2(ZBTB24):c.1192C>T (p.Arg398Ter)SNV Pathogenic 650017 6:109797390-109797390 6:109476187-109476187
7 ZBTB24 NM_014797.2(ZBTB24):c.47C>G (p.Ser16Ter)SNV Pathogenic 598541 rs370370334 6:109803183-109803183 6:109481980-109481980
8 ZBTB24 NM_014797.2(ZBTB24):c.1322A>G (p.Lys441Arg)SNV Uncertain significance 640298 6:109788904-109788904 6:109467701-109467701
9 ZBTB24 NM_014797.2(ZBTB24):c.943A>G (p.Ser315Gly)SNV Uncertain significance 646171 6:109802287-109802287 6:109481084-109481084
10 ZBTB24 NM_014797.2(ZBTB24):c.883C>T (p.Arg295Cys)SNV Uncertain significance 654207 6:109802347-109802347 6:109481144-109481144
11 ZBTB24 NM_014797.2(ZBTB24):c.788A>G (p.Lys263Arg)SNV Uncertain significance 653843 6:109802442-109802442 6:109481239-109481239
12 ZBTB24 NM_014797.2(ZBTB24):c.762C>T (p.Ser254=)SNV Uncertain significance 644907 6:109802468-109802468 6:109481265-109481265
13 ZBTB24 NM_014797.2(ZBTB24):c.356A>G (p.Tyr119Cys)SNV Uncertain significance 640347 6:109802874-109802874 6:109481671-109481671
14 ZBTB24 NM_014797.2(ZBTB24):c.334A>G (p.Thr112Ala)SNV Uncertain significance 647321 6:109802896-109802896 6:109481693-109481693
15 ZBTB24 NM_014797.2(ZBTB24):c.1750A>T (p.Met584Leu)SNV Uncertain significance 539534 rs139491074 6:109787398-109787398 6:109466195-109466195
16 ZBTB24 NM_014797.2(ZBTB24):c.1237C>T (p.Arg413Cys)SNV Uncertain significance 539531 rs149690823 6:109796653-109796653 6:109475450-109475450
17 ZBTB24 NM_014797.2(ZBTB24):c.1154A>G (p.Lys385Arg)SNV Uncertain significance 539530 rs371071024 6:109797428-109797428 6:109476225-109476225
18 ZBTB24 NM_014797.2(ZBTB24):c.730G>C (p.Glu244Gln)SNV Uncertain significance 539533 rs113516976 6:109802500-109802500 6:109481297-109481297
19 ZBTB24 NM_014797.2(ZBTB24):c.860A>G (p.Lys287Arg)SNV Uncertain significance 539532 rs1456427014 6:109802370-109802370 6:109481167-109481167
20 ZBTB24 NM_014797.2(ZBTB24):c.1666G>A (p.Val556Ile)SNV Uncertain significance 472201 rs778110573 6:109787482-109787482 6:109466279-109466279
21 ZBTB24 NM_001286613.1(MICAL1):c.-174A>GSNV Uncertain significance 539535 rs1554227574 6:109787054-109787054 6:109465851-109465851
22 ZBTB24 NM_014797.2(ZBTB24):c.439G>T (p.Val147Leu)SNV Uncertain significance 539529 rs766594494 6:109802791-109802791 6:109481588-109481588
23 ZBTB24 NM_001286613.1(MICAL1):c.-200A>GSNV Uncertain significance 572865 rs756260680 6:109787080-109787080 6:109465877-109465877
24 ZBTB24 NM_014797.2(ZBTB24):c.767G>A (p.Arg256Gln)SNV Uncertain significance 577750 rs1023323966 6:109802463-109802463 6:109481260-109481260
25 ZBTB24 NM_014797.2(ZBTB24):c.109T>C (p.Cys37Arg)SNV Uncertain significance 568130 rs1562305271 6:109803121-109803121 6:109481918-109481918
26 ZBTB24 NM_014797.2(ZBTB24):c.1969G>A (p.Glu657Lys)SNV Uncertain significance 572801 rs1222795316 6:109787179-109787179 6:109465976-109465976
27 ZBTB24 NM_014797.2(ZBTB24):c.1597G>C (p.Val533Leu)SNV Uncertain significance 574658 rs779741867 6:109787551-109787551 6:109466348-109466348
28 ZBTB24 NM_014797.2(ZBTB24):c.784G>A (p.Val262Ile)SNV Uncertain significance 569180 rs540553715 6:109802446-109802446 6:109481243-109481243
29 ZBTB24 NM_014797.2(ZBTB24):c.301G>A (p.Ala101Thr)SNV Uncertain significance 570181 rs144189559 6:109802929-109802929 6:109481726-109481726
30 ZBTB24 NM_014797.2(ZBTB24):c.1811A>G (p.Asn604Ser)SNV Uncertain significance 577255 rs767566292 6:109787337-109787337 6:109466134-109466134
31 ZBTB24 NM_014797.2(ZBTB24):c.235C>T (p.Leu79=)SNV Likely benign 539539 rs746668886 6:109802995-109802995 6:109481792-109481792
32 ZBTB24 NM_014797.2(ZBTB24):c.51C>T (p.Asp17=)SNV Likely benign 539537 rs376284623 6:109803179-109803179 6:109481976-109481976
33 ZBTB24 NM_014797.2(ZBTB24):c.1552G>A (p.Ala518Thr)SNV Benign 472200 rs2232448 6:109787596-109787596 6:109466393-109466393
34 ZBTB24 NM_014797.2(ZBTB24):c.1701C>T (p.Pro567=)SNV Benign 472202 rs2232449 6:109787447-109787447 6:109466244-109466244
35 ZBTB24 NM_014797.2(ZBTB24):c.579G>A (p.Gln193=)SNV Benign 472203 rs2227263 6:109802651-109802651 6:109481448-109481448

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2:

73
# Symbol AA change Variation ID SNP ID
1 ZBTB24 p.Cys408Gly VAR_065846 rs387907105

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

Search GEO for disease gene expression data for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2.

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

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

Molecular functions related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription regulatory region DNA binding GO:0044212 8.62 ZBTB24 CDK5RAP2

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

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