ICF2
MCID: IMM056
MIFTS: 35

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 57 12 72 29 6 15 70
Icf2 57 72
Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome, Type 2 39
Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome-2 13
Icf Syndrome 2 12

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
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® : 57 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) (Updated 20-May-2021)

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 intellectual disability and high palate

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

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
hypertelorism
epicanthal folds

Head And Neck Ears:
low-set ears

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 Face:
retrognathia
round face
small chin

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 (Updated 20-May-2021)

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 25)
# 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 6 57
21906047 2012
2
Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. 57 6 61
21596365 2011
3
Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects. 61 57
23486536 2013
4
Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). 57
17893117 2008
5
Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome. 61
32865561 2020
6
A young girl with hypogammaglobulinemia and granulomatous hepatitis caused by a novel mutation in ZBTB24 gene: A case based analysis. 61
32061411 2020
7
The gene mutations and subtelomeric DNA methylation in immunodeficiency, centromeric instability and facial anomalies syndrome. 61
31476899 2019
8
A functional assay to classify ZBTB24 missense variants of unknown significance. 61
31066130 2019
9
ZBTB24 regulates the apoptosis of human T cells via CDCA7/TRAIL-receptor axis. 61
31030944 2019
10
EBV-Related Hodgkin Lymphoma in an ICF2 Patient: Is EBV Susceptibility a Hallmark of This ICF Subtype? 61
30719684 2019
11
Progressive Immunodeficiency with Gradual Depletion of B and CD4⁺ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2). 61
30987377 2019
12
Complete photodissociation dynamics of CF2I2 in solution. 61
30882121 2019
13
Clinical and Immunological Characterization of ICF Syndrome in Japan. 61
30353301 2018
14
Subtelomeric methylation distinguishes between subtypes of Immunodeficiency, Centromeric instability and Facial anomalies syndrome. 61
30010917 2018
15
Comparative methylome analysis of ICF patients identifies heterochromatin loci that require ZBTB24, CDCA7 and HELLS for their methylated state. 61
29659838 2018
16
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
17
Expanding the mutation spectrum in ICF syndrome: Evidence for a gender bias in ICF2. 61
28128455 2017
18
Estimation of inbreeding depression on female fertility in the Finnish Ayrshire population. 61
28748554 2017
19
Hematopoietic Stem Cell Transplantation in a Patient With ICF2 Syndrome Presenting With EBV-Induced Hemophagocytic Lymphohystiocytosis. 61
27326813 2016
20
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
21
Genetic, Cellular and Clinical Features of ICF Syndrome: a French National Survey. 61
26851945 2016
22
Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2). 61
25330735 2014
23
Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients. 61
23739126 2013
24
Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome, due to ZBTB24 mutations, presenting with large cerebral cyst. 61
22786748 2012
25
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:

6 (show top 50) (show all 115)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ZBTB24 NM_014797.2(ZBTB24):c.958C>T (p.Arg320Ter) SNV Pathogenic 31093 rs387907104 GRCh37: 6:109798128-109798128
GRCh38: 6:109476925-109476925
2 ZBTB24 NM_014797.2(ZBTB24):c.47C>G (p.Ser16Ter) SNV Pathogenic 598541 rs370370334 GRCh37: 6:109803183-109803183
GRCh38: 6:109481980-109481980
3 ZBTB24 NM_014797.2(ZBTB24):c.833C>G (p.Ser278Ter) SNV Pathogenic 31095 rs1582683374 GRCh37: 6:109802397-109802397
GRCh38: 6:109481194-109481194
4 ZBTB24 NM_014797.2(ZBTB24):c.1222T>G (p.Cys408Gly) SNV Pathogenic 31096 rs387907105 GRCh37: 6:109796668-109796668
GRCh38: 6:109475465-109475465
5 ZBTB24 NM_014797.2(ZBTB24):c.396_397del (p.His132fs) Deletion Pathogenic 40181 rs1562305058 GRCh37: 6:109802833-109802834
GRCh38: 6:109481630-109481631
6 ZBTB24 NM_014797.2(ZBTB24):c.1192C>T (p.Arg398Ter) SNV Pathogenic 650017 rs867580676 GRCh37: 6:109797390-109797390
GRCh38: 6:109476187-109476187
7 ZBTB24 NM_014797.3(ZBTB24):c.888dup (p.Lys297Ter) Duplication Pathogenic 951999 GRCh37: 6:109802341-109802342
GRCh38: 6:109481138-109481139
8 ZBTB24 NM_014797.2(ZBTB24):c.1369C>T (p.Arg457Ter) SNV Likely pathogenic 31097 rs387907106 GRCh37: 6:109788857-109788857
GRCh38: 6:109467654-109467654
9 ZBTB24 NM_014797.2(ZBTB24):c.439G>T (p.Val147Leu) SNV Uncertain significance 539529 rs766594494 GRCh37: 6:109802791-109802791
GRCh38: 6:109481588-109481588
10 ZBTB24 NM_014797.2(ZBTB24):c.1154A>G (p.Lys385Arg) SNV Uncertain significance 539530 rs371071024 GRCh37: 6:109797428-109797428
GRCh38: 6:109476225-109476225
11 ZBTB24 NM_014797.2(ZBTB24):c.1237C>T (p.Arg413Cys) SNV Uncertain significance 539531 rs149690823 GRCh37: 6:109796653-109796653
GRCh38: 6:109475450-109475450
12 ZBTB24 NM_014797.2(ZBTB24):c.860A>G (p.Lys287Arg) SNV Uncertain significance 539532 rs1456427014 GRCh37: 6:109802370-109802370
GRCh38: 6:109481167-109481167
13 ZBTB24 NM_014797.2(ZBTB24):c.730G>C (p.Glu244Gln) SNV Uncertain significance 539533 rs113516976 GRCh37: 6:109802500-109802500
GRCh38: 6:109481297-109481297
14 ZBTB24 NM_014797.2(ZBTB24):c.1750A>T (p.Met584Leu) SNV Uncertain significance 539534 rs139491074 GRCh37: 6:109787398-109787398
GRCh38: 6:109466195-109466195
15 MICAL1 , ZBTB24 NM_014797.2(ZBTB24):c.2094A>G (p.Ter698Trp) SNV Uncertain significance 539535 rs1554227574 GRCh37: 6:109787054-109787054
GRCh38: 6:109465851-109465851
16 ZBTB24 NM_014797.2(ZBTB24):c.788A>G (p.Lys263Arg) SNV Uncertain significance 653843 rs148296427 GRCh37: 6:109802442-109802442
GRCh38: 6:109481239-109481239
17 ZBTB24 NM_014797.2(ZBTB24):c.883C>T (p.Arg295Cys) SNV Uncertain significance 654207 rs773712148 GRCh37: 6:109802347-109802347
GRCh38: 6:109481144-109481144
18 ZBTB24 NM_014797.2(ZBTB24):c.109T>C (p.Cys37Arg) SNV Uncertain significance 568130 rs1562305271 GRCh37: 6:109803121-109803121
GRCh38: 6:109481918-109481918
19 ZBTB24 NM_014797.2(ZBTB24):c.784G>A (p.Val262Ile) SNV Uncertain significance 569180 rs540553715 GRCh37: 6:109802446-109802446
GRCh38: 6:109481243-109481243
20 ZBTB24 NM_014797.2(ZBTB24):c.301G>A (p.Ala101Thr) SNV Uncertain significance 570181 rs144189559 GRCh37: 6:109802929-109802929
GRCh38: 6:109481726-109481726
21 ZBTB24 NM_014797.2(ZBTB24):c.1969G>A (p.Glu657Lys) SNV Uncertain significance 572801 rs1222795316 GRCh37: 6:109787179-109787179
GRCh38: 6:109465976-109465976
22 MICAL1 , ZBTB24 NM_014797.2(ZBTB24):c.2068A>G (p.Thr690Ala) SNV Uncertain significance 572865 rs756260680 GRCh37: 6:109787080-109787080
GRCh38: 6:109465877-109465877
23 ZBTB24 NM_014797.2(ZBTB24):c.1597G>C (p.Val533Leu) SNV Uncertain significance 574658 rs779741867 GRCh37: 6:109787551-109787551
GRCh38: 6:109466348-109466348
24 ZBTB24 NM_014797.2(ZBTB24):c.1811A>G (p.Asn604Ser) SNV Uncertain significance 577255 rs767566292 GRCh37: 6:109787337-109787337
GRCh38: 6:109466134-109466134
25 ZBTB24 NM_014797.2(ZBTB24):c.767G>A (p.Arg256Gln) SNV Uncertain significance 577750 rs1023323966 GRCh37: 6:109802463-109802463
GRCh38: 6:109481260-109481260
26 ZBTB24 NM_014797.2(ZBTB24):c.1322A>G (p.Lys441Arg) SNV Uncertain significance 640298 rs373035965 GRCh37: 6:109788904-109788904
GRCh38: 6:109467701-109467701
27 ZBTB24 NM_014797.2(ZBTB24):c.356A>G (p.Tyr119Cys) SNV Uncertain significance 640347 rs774995879 GRCh37: 6:109802874-109802874
GRCh38: 6:109481671-109481671
28 ZBTB24 NM_014797.2(ZBTB24):c.762C>T (p.Ser254=) SNV Uncertain significance 644907 rs374544868 GRCh37: 6:109802468-109802468
GRCh38: 6:109481265-109481265
29 ZBTB24 NM_014797.2(ZBTB24):c.943A>G (p.Ser315Gly) SNV Uncertain significance 646171 rs759942793 GRCh37: 6:109802287-109802287
GRCh38: 6:109481084-109481084
30 ZBTB24 NM_014797.2(ZBTB24):c.334A>G (p.Thr112Ala) SNV Uncertain significance 647321 rs567279982 GRCh37: 6:109802896-109802896
GRCh38: 6:109481693-109481693
31 ZBTB24 NM_014797.2(ZBTB24):c.1666G>A (p.Val556Ile) SNV Uncertain significance 472201 rs778110573 GRCh37: 6:109787482-109787482
GRCh38: 6:109466279-109466279
32 ZBTB24 NM_014797.3(ZBTB24):c.430G>C (p.Gly144Arg) SNV Uncertain significance 837750 GRCh37: 6:109802800-109802800
GRCh38: 6:109481597-109481597
33 MICAL1 , ZBTB24 NM_014797.3(ZBTB24):c.2078G>A (p.Gly693Asp) SNV Uncertain significance 839315 GRCh37: 6:109787070-109787070
GRCh38: 6:109465867-109465867
34 ZBTB24 NM_014797.3(ZBTB24):c.1155A>G (p.Lys385=) SNV Uncertain significance 839785 GRCh37: 6:109797427-109797427
GRCh38: 6:109476224-109476224
35 ZBTB24 NM_014797.3(ZBTB24):c.1538G>A (p.Ser513Asn) SNV Uncertain significance 841861 GRCh37: 6:109787610-109787610
GRCh38: 6:109466407-109466407
36 ZBTB24 NM_014797.3(ZBTB24):c.99A>T (p.Lys33Asn) SNV Uncertain significance 842298 GRCh37: 6:109803131-109803131
GRCh38: 6:109481928-109481928
37 ZBTB24 NM_014797.3(ZBTB24):c.1748A>G (p.Asn583Ser) SNV Uncertain significance 844207 GRCh37: 6:109787400-109787400
GRCh38: 6:109466197-109466197
38 ZBTB24 NM_014797.3(ZBTB24):c.401C>A (p.Ser134Tyr) SNV Uncertain significance 844350 GRCh37: 6:109802829-109802829
GRCh38: 6:109481626-109481626
39 ZBTB24 NM_014797.3(ZBTB24):c.1936G>A (p.Glu646Lys) SNV Uncertain significance 848363 GRCh37: 6:109787212-109787212
GRCh38: 6:109466009-109466009
40 ZBTB24 NM_014797.3(ZBTB24):c.855G>T (p.Arg285Ser) SNV Uncertain significance 849183 GRCh37: 6:109802375-109802375
GRCh38: 6:109481172-109481172
41 ZBTB24 NM_014797.3(ZBTB24):c.1602G>C (p.Arg534Ser) SNV Uncertain significance 852827 GRCh37: 6:109787546-109787546
GRCh38: 6:109466343-109466343
42 ZBTB24 NM_014797.3(ZBTB24):c.730G>A (p.Glu244Lys) SNV Uncertain significance 855304 GRCh37: 6:109802500-109802500
GRCh38: 6:109481297-109481297
43 ZBTB24 NM_014797.3(ZBTB24):c.1280C>A (p.Thr427Lys) SNV Uncertain significance 857324 GRCh37: 6:109796610-109796610
GRCh38: 6:109475407-109475407
44 ZBTB24 NM_014797.3(ZBTB24):c.1046C>T (p.Pro349Leu) SNV Uncertain significance 860921 GRCh37: 6:109798040-109798040
GRCh38: 6:109476837-109476837
45 ZBTB24 NM_014797.3(ZBTB24):c.1753A>T (p.Thr585Ser) SNV Uncertain significance 936713 GRCh37: 6:109787395-109787395
GRCh38: 6:109466192-109466192
46 ZBTB24 NM_014797.3(ZBTB24):c.952+6G>A SNV Uncertain significance 940797 GRCh37: 6:109802272-109802272
GRCh38: 6:109481069-109481069
47 ZBTB24 NM_014797.3(ZBTB24):c.376A>G (p.Thr126Ala) SNV Uncertain significance 940969 GRCh37: 6:109802854-109802854
GRCh38: 6:109481651-109481651
48 ZBTB24 NM_014797.3(ZBTB24):c.620T>C (p.Leu207Pro) SNV Uncertain significance 941092 GRCh37: 6:109802610-109802610
GRCh38: 6:109481407-109481407
49 ZBTB24 NM_014797.3(ZBTB24):c.1498G>T (p.Ala500Ser) SNV Uncertain significance 941167 GRCh37: 6:109787650-109787650
GRCh38: 6:109466447-109466447
50 ZBTB24 NM_014797.3(ZBTB24):c.818A>G (p.Gln273Arg) SNV Uncertain significance 941962 GRCh37: 6:109802412-109802412
GRCh38: 6:109481209-109481209

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

72
# 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...

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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19 FMA
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33 ICD10 via Orphanet
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44 MeSH
45 MESH via Orphanet
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57 OMIM® (Updated 20-May-2021)
61 PubMed
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69 Tocris
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71 UMLS via Orphanet
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