Details of Disease

General Information of Disease (ID: DISKD3CW)

• Disease Name: CHARGE syndrome
• Synonyms: Charge association--coloboma, heart anomaly, choanal atresia, retardation, genital and Ear anomalies; coloboma, heart anomaly, choanal atresia, retardation, genital and ear anomalies; coloboma-heart defects-atresia choanae-retardation of growth and development-genitourinary problems-ear abnormalities syndrome; coloboma, heart malformation, choanal atresia, retardation of Growth and development, genital abnormalities, and Ear malformations (CHARGE) association; CHARGE association; Hall-Hittner syndrome; coloboma, heart defects, choanal atresia, retardation of Growth and development, genital abnormalities, and Ear anomalies association; CHARGE syndrome
• Definition: CHARGE syndrome is a multiple congenital anomaly syndrome characterized by the variable combination of multiple anomalies, mainly Coloboma; Choanal atresia/stenosis; Cranial nerve dysfunction; Characteristic ear anomalies (known as the major 4 C's).|This term's classification was reviewed in the context of the Strategic Refinement project (2023) and was determined to be excluded from the 'immune system disorder' (MONDO:0005046) ontology branch (https://orcid.org/0000-0001-8216-5084)
• Disease Hierarchy:
  DIS7667R: Multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome
  DIS6SVEE: Syndromic disease
  DISMT2VZ: Cardiogenetic disease
  DISEV092: Congenital hypogonadotropic hypogonadism
  DIS2IQBH: Neurocristopathy
  DISKD3CW: CHARGE syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0008965
  MESH ID: D058747
  UMLS CUI: C0265354
  OMIM ID: 214800
  MedGen ID: 75567
  Orphanet ID: 138
  SNOMED CT ID: 47535005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KCNQ2	TTPXI3S	moderate	Biomarker	[1]
SCN2A	TTLJTUF	moderate	Biomarker	[1]

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MTG1	OTC9U1LI	Limited	Genetic Variation	[2]
SEMA3E	OTD4S36H	Limited	Autosomal dominant	[3]
AFF2	OTMF1PZW	moderate	Biomarker	[1]
CAPRIN1	OTEJAMS3	moderate	Biomarker	[1]
FAM124B	OTL2A8O8	moderate	Biomarker	[4]
NRXN1	OTJN1JQA	moderate	Biomarker	[1]
RERE	OT3G4GBZ	moderate	Genetic Variation	[5]
CHD2	OTRKL6YC	Strong	Biomarker	[6]
CHD8	OTS7A6AF	Strong	Biomarker	[7]
COA1	OTHSX40F	Strong	Biomarker	[8]
FOXE1	OT5IR5IT	Strong	Genetic Variation	[9]
FOXN1	OTE80D6I	Strong	Altered Expression	[10]
GALNT3	OT7M67WT	Strong	Genetic Variation	[11]
GLUD1	OTXKOCUH	Strong	Genetic Variation	[12]
STATH	OTQHBHM9	Strong	Biomarker	[13]
CHD7	OTHNIZWZ	Definitive	Autosomal dominant	[14]

References

• [1] Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.Am J Hum Genet. 2013 Aug 8;93(2):249-63. doi: 10.1016/j.ajhg.2013.06.012. Epub 2013 Jul 11.
• [2] Glutamate dehydrogenase: Structure of a hyperinsulinism mutant, corrections to the atomic model, and insights into a regulatory site.Proteins. 2019 Jan;87(1):41-50. doi: 10.1002/prot.25620. Epub 2018 Nov 18.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] Identification and characterization of FAM124B as a novel component of a CHD7 and CHD8 containing complex.PLoS One. 2012;7(12):e52640. doi: 10.1371/journal.pone.0052640. Epub 2012 Dec 21.
• [5] Genotype-phenotype correlations in individuals with pathogenic RERE variants.Hum Mutat. 2018 May;39(5):666-675. doi: 10.1002/humu.23400. Epub 2018 Jan 25.
• [6] Deletion of the RMGA and CHD2 genes in a child with epilepsy and mental deficiency.Eur J Med Genet. 2012 Feb;55(2):132-4. doi: 10.1016/j.ejmg.2011.10.004. Epub 2011 Nov 25.
• [7] Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8.Proc Natl Acad Sci U S A. 2018 Aug 28;115(35):E8246-E8255. doi: 10.1073/pnas.1802620115. Epub 2018 Aug 14.
• [8] The mutation in Chd7 causes misexpression of Bmp4 and developmental defects in telencephalic midline.Am J Pathol. 2012 Aug;181(2):626-41. doi: 10.1016/j.ajpath.2012.05.006. Epub 2012 May 29.
• [9] FOXE1 gene mutation screening by multiplex PCR/DHPLC in CHARGE syndrome and syndromic and non-syndromic cleft palate.J Chromatogr B Analyt Technol Biomed Life Sci. 2006 May 19;836(1-2):39-46. doi: 10.1016/j.jchromb.2006.03.028. Epub 2006 Apr 11.
• [10] Chd7 Is Critical for Early T-Cell Development and Thymus Organogenesis in Zebrafish.Am J Pathol. 2018 Apr;188(4):1043-1058. doi: 10.1016/j.ajpath.2017.12.005. Epub 2018 Jan 31.
• [11] Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations.J Clin Endocrinol Metab. 2007 May;92(5):1943-7. doi: 10.1210/jc.2006-1825. Epub 2007 Feb 20.
• [12] Urinary alpha-ketoglutarate is elevated in patients with hyperinsulinism-hyperammonemia syndrome.Clin Chim Acta. 2004 Mar;341(1-2):23-6. doi: 10.1016/j.cccn.2003.10.023.
• [13] SNP genotyping to screen for a common deletion in CHARGE syndrome.BMC Med Genet. 2005 Feb 14;6:8. doi: 10.1186/1471-2350-6-8.
• [14] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.