Details of Disease

Disease Name

DiGeorge syndrome

hypoplasia of thymus and parathyroids; Takao VCF syndrome; third and fourth pharyngeal pouch syndrome; chromosome 22Q11.2 deletion syndrome; velocardiofacial syndrome; Catch22; VCF; velo-cardio-facial syndrome; DiGeorge syndrome chromosome region; Sphrintzen; Shprintzen syndrome; pharyngeal pouch syndrome; 22q11.2 Deletion syndrome; 22q deletion syndrome(s); DiGeorge syndrome; DiGeorge syndrome type 1; DGS1; DiGeorge's syndrome; DGS; DiGeorge anomaly; Di-George syndrome

Definition

A congenital anomaly characterized by immunodeficiency, abnormal facies, congenital heart disease, hypocalcemia, and increased susceptibility to infections. Pathologic characteristics include conotruncal abnormalities and absence or hypoplasia of thymus and parathyroid glands. DiGeorge syndrome is associated with abnormalities of chromosome 22. Also known as DiGeorge anomaly.

Disease Hierarchy

DISMT2VZ: Cardiogenetic disease

DISD715V: Hereditary neurological disease

DISMOPYM: 22q11.2 deletion syndrome

DIS2IQBH: Neurocristopathy

DISPG7T7: Congenital T-cell immunodeficiency

DIST1RKO: DiGeorge syndrome

Disease Identifiers

MONDO ID

MONDO_0008564

MESH ID

D004062

UMLS CUI

C0012236

OMIM ID

188400

MedGen ID

4297

SNOMED CT ID

767263007

General Information of Disease (ID: DIST1RKO)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SLC25A1	TTTD730	moderate	Genetic Variation	[1]
APOL1	TTDB8PW	Strong	Biomarker	[2]
CHRNA7	TTLA931	Strong	Genetic Variation	[3]
JMJD1C	TTBISK4	Strong	GermlineModifyingMutation	[4]
KAT6A	TT6O1J0	Strong	Biomarker	[5]
NAAA	TTMN4HY	Strong	Biomarker	[6]
SYVN1	TT8XKYM	Strong	Genetic Variation	[7]
FGF8	TTIUF3J	Definitive	Biomarker	[8]
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⏷ Show the Full List of 8 DTT(s)

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ALDH1A2	DEKN1H4	Strong	Biomarker	[9]
PRODH	DEVJIHS	Strong	Biomarker	[10]
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This Disease Is Related to 40 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SPECC1L	OT3WGZ73	Limited	Genetic Variation	[11]
FBXO7	OTGTN8TJ	Disputed	Altered Expression	[12]
CDC45	OT6NNLOD	moderate	Biomarker	[13]
DGCR2	OTEGL17Z	moderate	Biomarker	[14]
DGCR8	OT62LXE4	moderate	Genetic Variation	[15]
C19orf12	OTVSJ1AR	Strong	Biomarker	[16]
CECR2	OTF54V3W	Strong	Genetic Variation	[17]
CELF2	OTLJJ4VT	Strong	Genetic Variation	[18]
CHD7	OTHNIZWZ	Strong	Genetic Variation	[19]
CHRD	OTNM60Y1	Strong	Biomarker	[20]
CLTC	OTBFASMA	Strong	Biomarker	[21]
CPO	OTOIG8C9	Strong	Biomarker	[22]
CRKL	OTOYSD1R	Strong	Biomarker	[23]
DERL3	OTRZRT6Q	Strong	Genetic Variation	[7]
DGCR6L	OTE0Z7WM	Strong	Biomarker	[24]
DNAJC13	OTYAVVJ6	Strong	Biomarker	[16]
EYA1	OTHU807A	Strong	Genetic Variation	[25]
FOXI3	OTGQSH1Z	Strong	Biomarker	[26]
FOXN1	OTE80D6I	Strong	Genetic Variation	[26]
GNB1L	OTXSUD8R	Strong	Biomarker	[27]
GP1BB	OTD7XNLL	Strong	Biomarker	[28]
GSC2	OT1CO9ED	Strong	Genetic Variation	[29]
HIRA	OTON40EJ	Strong	Genetic Variation	[30]
HOXA3	OTIX5XFB	Strong	Biomarker	[31]
HTRA2	OTC7616F	Strong	Genetic Variation	[32]
LAMC1	OTIG527N	Strong	Biomarker	[33]
LZTR1	OTIDM6XO	Strong	Biomarker	[34]
MED15	OT0D0JVD	Strong	Biomarker	[35]
MYZAP	OTAZCNBT	Strong	Biomarker	[36]
NKX2-6	OTPPKGTE	Strong	Biomarker	[37]
NPLOC4	OTC1WUVF	Strong	Genetic Variation	[38]
PRDM9	OTWAHLUR	Strong	Genetic Variation	[39]
RAB39B	OTDCLLT0	Strong	Biomarker	[16]
RANBP1	OTQE226K	Strong	Biomarker	[40]
RREB1	OT62460U	Strong	GermlineModifyingMutation	[4]
SEC24C	OTMTJBQ1	Strong	GermlineModifyingMutation	[4]
SEPTIN5	OT6JTJBO	Strong	Biomarker	[41]
SLC7A4	OTAVC6QS	Strong	Biomarker	[42]
DGCR6	OTBOXM33	Definitive	Biomarker	[43]
TBX1	OTQLBPRA	Definitive	Autosomal dominant	[44]
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⏷ Show the Full List of 40 DOT(s)

References

1	The human mitochondrial citrate transporter gene (SLC20A3) maps to chromosome band 22q11 within a region implicated in DiGeorge syndrome, velo-cardio-facial syndrome and schizophrenia.Hum Genet. 1996 Jul;98(1):113-5. doi: 10.1007/s004390050169.
2	Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22.Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4680-5. doi: 10.1073/pnas.032069099.
3	NAHR-mediated copy-number variants in a clinical population: mechanistic insights into both genomic disorders and Mendelizing traits.Genome Res. 2013 Sep;23(9):1395-409. doi: 10.1101/gr.152454.112. Epub 2013 May 8.
4	Histone Modifier Genes Alter Conotruncal Heart Phenotypes in 22q11.2 Deletion Syndrome.Am J Hum Genet. 2015 Dec 3;97(6):869-77. doi: 10.1016/j.ajhg.2015.10.013. Epub 2015 Nov 19.
5	MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome.Dev Cell. 2012 Sep 11;23(3):652-63. doi: 10.1016/j.devcel.2012.07.010. Epub 2012 Aug 23.
6	Eltrombopag Therapy in Children With Rare Disorders Associated With Thrombocytopenia.J Pediatr Hematol Oncol. 2020 Mar;42(2):113-117. doi: 10.1097/MPH.0000000000001528.
7	Features of di George syndrome in a child with 45,XX,-3,-22,+der(3),t(3;22)(p25;q11).J Med Genet. 1987 Apr;24(4):225-7. doi: 10.1136/jmg.24.4.225.
8	Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome.Dev Cell. 2006 Jan;10(1):81-92. doi: 10.1016/j.devcel.2005.12.002.
9	Decreased embryonic retinoic acid synthesis results in a DiGeorge syndrome phenotype in newborn mice.Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1763-8. doi: 10.1073/pnas.0437920100. Epub 2003 Jan 31.
10	Functional polymorphisms in PRODH are associated with risk and protection for schizophrenia and fronto-striatal structure and function.PLoS Genet. 2008 Nov;4(11):e1000252. doi: 10.1371/journal.pgen.1000252. Epub 2008 Nov 7.
11	Mutations in SPECC1L, encoding sperm antigen with calponin homology and coiled-coil domains 1-like, are found in some cases of autosomal dominant Opitz G/BBB syndrome.J Med Genet. 2015 Feb;52(2):104-10. doi: 10.1136/jmedgenet-2014-102677. Epub 2014 Nov 20.
12	Opposing effects on the cell cycle of T lymphocytes by Fbxo7 via Cdk6 and p27.Cell Mol Life Sci. 2017 Apr;74(8):1553-1566. doi: 10.1007/s00018-016-2427-3. Epub 2016 Dec 3.
13	UFD1L and CDC45L: a role in DiGeorge syndrome and related phenotypes?.Trends Genet. 1999 Jul;15(7):251-4. doi: 10.1016/s0168-9525(99)01772-2.
14	The Candidate Schizophrenia Risk Gene DGCR2 Regulates Early Steps of Corticogenesis.Biol Psychiatry. 2018 Apr 15;83(8):692-706. doi: 10.1016/j.biopsych.2017.11.015. Epub 2017 Nov 21.
15	Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation.Sci Rep. 2018 Jan 23;8(1):1468. doi: 10.1038/s41598-018-19660-z.
16	Neuropathology of genetic synucleinopathies with parkinsonism: Review of the literature.Mov Disord. 2017 Nov;32(11):1504-1523. doi: 10.1002/mds.27193.
17	Prenatal detection and characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 22 with apparently normal phenotype.Prenat Diagn. 2006 Oct;26(10):898-902. doi: 10.1002/pd.1520.
18	Expression and mutation analysis of BRUNOL3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p.J Mol Med (Berl). 2002 Jul;80(7):431-42. doi: 10.1007/s00109-002-0331-9. Epub 2002 Apr 4.
19	Establishment of immunity against Epstein-Barr virus infection in a patient with CHARGE/complete DiGeorge syndrome after peripheral blood lymphocyte transfusion.Pediatr Transplant. 2019 Jun;23(4):e13424. doi: 10.1111/petr.13424. Epub 2019 Apr 29.
20	The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge syndrome.Development. 2003 Aug;130(15):3567-78. doi: 10.1242/dev.00581.
21	Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome.Hum Mol Genet. 1996 May;5(5):617-24. doi: 10.1093/hmg/5.5.617.
22	Prevalence of duplications and deletions of the 22q11 DiGeorge syndrome region in a population-based sample of infants with cleft palate.Am J Med Genet A. 2007 Jan 15;143A(2):129-34. doi: 10.1002/ajmg.a.31445.
23	22q11.2 duplications in a UK cohort with bladder exstrophy-epispadias complex.Am J Med Genet A. 2019 Mar;179(3):404-409. doi: 10.1002/ajmg.a.61032. Epub 2019 Jan 9.
24	Biochemical characterisation of the proteins encoded by the DiGeorge critical region 6 (DGCR6) genes.Hum Genet. 2005 Jun;117(1):70-80. doi: 10.1007/s00439-005-1267-2. Epub 2005 Apr 9.
25	Six1 and Eya1 are critical regulators of peri-cloacal mesenchymal progenitors during genitourinary tract development.Dev Biol. 2011 Dec 1;360(1):186-94. doi: 10.1016/j.ydbio.2011.09.020. Epub 2011 Sep 24.
26	Recurrent microdeletions at chromosome 2p11.2 are associated with thymic hypoplasia and features resembling DiGeorge syndrome.J Allergy Clin Immunol. 2020 Jan;145(1):358-367.e2. doi: 10.1016/j.jaci.2019.09.020. Epub 2019 Oct 7.
27	GNB1L, a gene deleted in the critical region for DiGeorge syndrome on 22q11, encodes a G-protein beta-subunit-like polypeptide.Biochim Biophys Acta. 2000 Nov 15;1494(1-2):185-8. doi: 10.1016/s0167-4781(00)00189-5.
28	Heterozygous loss of platelet glycoprotein (GP) Ib-V-IX variably affects platelet function in velocardiofacial syndrome (VCFS) patients.Thromb Haemost. 2007 Dec;98(6):1298-308.
29	Goosecoid-like, a gene deleted in DiGeorge and velocardiofacial syndromes, recognizes DNA with a bicoid-like specificity and is expressed in the developing mouse brain.Hum Mol Genet. 1998 Sep;7(9):1497-505. doi: 10.1093/hmg/7.9.1497.
30	Multiplexed quantitative real-time PCR to detect 22q11.2 deletion in patients with congenital heart disease.Physiol Genomics. 2010 Sep;42A(1):52-60. doi: 10.1152/physiolgenomics.00073.2010. Epub 2010 Jun 15.
31	Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function.Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10555-60. doi: 10.1073/pnas.1005129107. Epub 2010 May 24.
32	Erratum to "Mitochondrial Serine Protease HTRA2 p.G399S in a Female with Di George Syndrome and Parkinson's Disease".Parkinsons Dis. 2018 Sep 9;2018:5956437. doi: 10.1155/2018/5956437. eCollection 2018.
33	Isolation of a novel gene from the DiGeorge syndrome critical region with homology to Drosophila gdl and to human LAMC1 genes.Hum Mol Genet. 1996 May;5(5):633-8. doi: 10.1093/hmg/5.5.633.
34	Isolation and characterization of a novel gene deleted in DiGeorge syndrome.Hum Mol Genet. 1995 Apr;4(4):541-9. doi: 10.1093/hmg/4.4.541.
35	Isolation and characterization of a novel gene from the DiGeorge chromosomal region that encodes for a mediator subunit.Genomics. 2001 Jun 15;74(3):320-32. doi: 10.1006/geno.2001.6566.
36	Patients affected by a new variant of endemic pemphigus foliaceus have autoantibodies colocalizing with MYZAP, p0071, desmoplakins 1-2 and ARVCF, causing renal damage.Clin Exp Dermatol. 2018 Aug;43(6):692-702. doi: 10.1111/ced.13566. Epub 2018 May 16.
37	Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation.J Med Genet. 2014 Apr;51(4):268-70. doi: 10.1136/jmedgenet-2013-102100. Epub 2014 Jan 13.
38	Cloning and characterization of the gene encoding human NPL4, a protein interacting with the ubiquitin fusion-degradation protein (UFD1L).Gene. 2001 Sep 5;275(1):39-46. doi: 10.1016/s0378-1119(01)00649-7.
39	Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction.Hum Genet. 2012 Sep;131(9):1519-24. doi: 10.1007/s00439-012-1180-4. Epub 2012 May 30.
40	RanBP1, a velocardiofacial/DiGeorge syndrome candidate gene, is expressed at sites of mesenchymal/epithelial induction.Mech Dev. 2002 Feb;111(1-2):177-80. doi: 10.1016/s0925-4773(01)00616-5.
41	Expression of Cdcrel-1 (Pnutl1), a gene frequently deleted in velo-cardio-facial syndrome/DiGeorge syndrome.Mech Dev. 2000 Aug;96(1):121-4. doi: 10.1016/s0925-4773(00)00370-1.
42	The gene encoding a cationic amino acid transporter (SLC7A4) maps to the region deleted in the velocardiofacial syndrome.Genomics. 1998 Apr 15;49(2):230-6. doi: 10.1006/geno.1998.5252.
43	GABA(B) receptor subunit 1 binds to proteins affected in 22q11 deletion syndrome.Biochem Biophys Res Commun. 2010 Mar 5;393(2):185-9. doi: 10.1016/j.bbrc.2009.12.120. Epub 2009 Dec 28.
44	Role of TBX1 in human del22q11.2 syndrome. Lancet. 2003 Oct 25;362(9393):1366-73. doi: 10.1016/s0140-6736(03)14632-6.