Details of Disease

General Information of Disease (ID: DISC91LV)

• Disease Name: Hyper-IgM syndrome type 1
• Synonyms: immunodeficiency 3; hyper IgM immunodeficiency, X-linked; immunodeficiency with hyper IgM type 1; X-linked hyper IgM syndrome; hyper IgM syndrome 1; hyper-IgM syndrome; CD40 ligand deficiency; hyper IgM syndrome; hyper-IgM immunodeficiency, X-linked; IHIS; hyper-IgM syndrome 1; XHIM; HIGM; immunodeficiency with hyper-IgM, type 1; hyper-IgM syndrome due to CD40L deficiency; Hyper IgM Syndromes; hyperimmunoglobulin M syndrome; HIGMX-1; X-linked hyper-IgM syndrome; XHIGM; hyper-IgM syndrome, X-linked; hyper-IgM syndrome due to CD40 ligand deficiency; HIGM1; hyper-IgM syndrome type 1; immunodeficiency, X-linked, with hyper-IgM, X-linked recessive
• Definition: The X-linked variant of the Hyper-IgM syndrome. The affected individuals are virtually always male, because males only have one X chromosome, received from their mothers. Their mothers are not symptomatic, even though they are carriers of the allele, because the trait is recessive. Male offspring of these women have a 50% chance of inheriting their mother's mutant allele.|This variant of the hyper-IgM syndrome is caused by mutation of the CD40LG gene. The genetic locus for this gene is Xq26. This gene codes for the CD40 ligand, which is expressed on T cells. When the CD40 ligand binds CD40 on B cells, then the B cell switches from producing IgM to producing IgA or IgG.
• Disease Hierarchy:
  DISLWPN6: Hyper-IgM syndrome
  DIS3PN9X: X-linked disease
  DISC91LV: Hyper-IgM syndrome type 1
• Disease Identifiers:
  MONDO ID: MONDO_0010626
  MESH ID: D053307
  UMLS CUI: C0398689
  OMIM ID: 308230
  MedGen ID: 96019
  Orphanet ID: 101088
  SNOMED CT ID: 403835002

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AICDA	TTKRTP6	Disputed	Genetic Variation	[1]
CD27	TTDO1MV	Strong	Biomarker	[2]
FCER2	TTCH6MU	Strong	Altered Expression	[3]
CD40LG	TTIJP3Q	Definitive	X-linked	[4]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MRFAP1	OT1AI7NF	moderate	Genetic Variation	[5]
SWAP70	OTPHT2QD	moderate	Biomarker	[6]
CHI3L1	OT2Z7VJH	Strong	Genetic Variation	[7]
IKBKG	OTNWJWSD	Strong	Genetic Variation	[8]
CD40LG	OT75Z6A6	Definitive	X-linked	[4]

References

• [1] Respiratory Complications in Patients with Hyper IgM Syndrome.J Clin Immunol. 2019 Aug;39(6):557-568. doi: 10.1007/s10875-019-00650-3. Epub 2019 Jun 11.
• [2] Analysis of somatic hypermutation in X-linked hyper-IgM syndrome shows specific deficiencies in mutational targeting.Blood. 2009 Apr 16;113(16):3706-15. doi: 10.1182/blood-2008-10-183632. Epub 2008 Nov 20.
• [3] c-Rel plays a key role in deficient activation of B cells from a non-X-linked hyper-IgM patient.Blood. 2006 Dec 1;108(12):3769-76. doi: 10.1182/blood-2006-03-008839. Epub 2006 Aug 8.
• [4] 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.
• [5] The molecular basis of X-linked agammaglobulinemia, hyper-IgM syndrome, and severe combined immunodeficiency in humans.Curr Opin Hematol. 1994 Jan;1(1):12-8.
• [6] Analysis of SWAP-70 as a candidate gene for non-X-linked hyper IgM syndrome and common variable immunodeficiency.Clin Immunol. 2001 Dec;101(3):270-5. doi: 10.1006/clim.2001.5116.
• [7] Leukocyte transfusion-associated granulocyte responses in a patient with X-linked hyper-IgM syndrome.J Clin Immunol. 1998 Nov;18(6):430-9. doi: 10.1023/a:1023286807853.
• [8] Clinical features and genetic analysis of Taiwanese patients with the hyper IgM syndrome phenotype.Pediatr Infect Dis J. 2013 Sep;32(9):1010-6. doi: 10.1097/INF.0b013e3182936280.