Details of Disease

General Information of Disease (ID: DISQ5ZYP)

• Disease Name: Bruton-type agammaglobulinemia
• Synonyms: agammaglobulinemia, Bruton tyrosine kinase; Bruton's agammaglobulinemia; agammaglobulinemia, X-linked, type 1; agammaglobulinemia, BTK; agammaglobulinemia, X-linked; XLA; hypogammaglobulinemia, X-linked; immunodeficiency 1; Bruton type agammaglobulinemia; Bruton's X-linked agammaglobulinemia; agammaglobulinemia, X-linked 1, X-linked recessive; Bruton agammaglobulinemia tyrosine kinase deficiency; Bruton's type agammaglobulinemia; X-linked agammaglobulinemia; Bruton's Sex-linked agammaglobulinemia; BTK-deficiency; Bruton's agammaglobulinaemia; BTK deficiency; Bruton-type agammaglobulinemia
• Definition: X-linked agammaglobulinemia (XLA) is a clinically variable form of isolated agammaglobulinemia, an inherited immunodeficiency disorder, and is characterized in affected males by recurrent bacterial infections during infancy.
• Disease Hierarchy:
  DIS3W5M5: Isolated agammaglobulinemia
  DISQ5ZYP: Bruton-type agammaglobulinemia
• Disease Identifiers:
  MONDO ID: MONDO_0010421
  MESH ID: C537409
  UMLS CUI: C0221026
  OMIM ID: 300755
  MedGen ID: 65123
  Orphanet ID: 47
  SNOMED CT ID: 65880007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TLR8	TT8CWFK	Limited	Biomarker	[1]
TNFRSF17	TTZ3P4W	Limited	Altered Expression	[2]
CD19	TTW640A	Strong	Altered Expression	[3]
FCER2	TTCH6MU	Strong	Altered Expression	[4]
BTK	TTGM6VW	Definitive	X-linked	[5]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ACP3	DEDW5H6	Limited	Altered Expression	[6]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AKAP17A	OT2CEJW4	Strong	Genetic Variation	[7]
BLNK	OTSSPF6F	Strong	Genetic Variation	[8]
CD79A	OTOJC8DV	Strong	Genetic Variation	[9]
DNALI1	OTTB3L8N	Strong	Biomarker	[10]
IGLL1	OTRTNVOG	Strong	Genetic Variation	[9]
IL2RG	OTRZ3OMY	Strong	Genetic Variation	[11]
PIK3R1	OT5BZ1J9	Strong	Genetic Variation	[12]
PLEK	OTB73XXA	Strong	Genetic Variation	[13]
RBMS1	OTD13PJN	Strong	Biomarker	[14]
RNF216	OTR1XEZ3	Strong	Altered Expression	[15]
TMEM132D	OTV6I4Z0	Strong	Biomarker	[14]
BTK	OTG3CDVK	Definitive	X-linked	[5]

References

• [1] Impaired Toll-like receptor 8-mediated IL-6 and TNF-alpha production in antigen-presenting cells from patients with X-linked agammaglobulinemia.Blood. 2007 Mar 15;109(6):2553-6. doi: 10.1182/blood-2006-07-037960. Epub 2006 Nov 7.
• [2] Serum B-Cell Maturation Antigen (BCMA) Levels Differentiate Primary Antibody Deficiencies.J Allergy Clin Immunol Pract. 2020 Jan;8(1):283-291.e1. doi: 10.1016/j.jaip.2019.08.012. Epub 2019 Aug 17.
• [3] Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe: a cohort study.Mol Immunol. 2009 Jun;46(10):2140-6. doi: 10.1016/j.molimm.2009.03.012. Epub 2009 May 5.
• [4] Functional analysis of peripheral blood B cells in patients with X-linked agammaglobulinemia.J Immunol. 1998 Oct 15;161(8):3925-9.
• [5] 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.
• [6] Ecto-5'-nucleotidase activity in T and B lymphocytes from normal subjects and patients with congenital X-linked agammaglobulinemia.J Immunol. 1979 Dec;123(6):2475-8.
• [7] Atypical X-linked agammaglobulinaemia caused by a novel BTK mutation in a selective immunoglobulin M deficiency patient.BMC Pediatr. 2013 Sep 27;13:150. doi: 10.1186/1471-2431-13-150.
• [8] Stability and peptide binding specificity of Btk SH2 domain: molecular basis for X-linked agammaglobulinemia.Protein Sci. 2000 Dec;9(12):2377-85. doi: 10.1110/ps.9.12.2377.
• [9] Novel Igalpha (CD79a) gene mutation in a Turkish patient with B cell-deficient agammaglobulinemia. Am J Med Genet. 2002 Apr 1;108(4):333-6. doi: 10.1002/ajmg.10296.
• [10] Bacteremia caused by a novel helicobacter species in a 28-year-old man with X-linked agammaglobulinemia.J Clin Microbiol. 2010 Dec;48(12):4672-6. doi: 10.1128/JCM.01350-10. Epub 2010 Sep 29.
• [11] Close linkage of the locus for X chromosome-linked severe combined immunodeficiency to polymorphic DNA markers in Xq11-q13.Proc Natl Acad Sci U S A. 1987 Nov;84(21):7576-9. doi: 10.1073/pnas.84.21.7576.
• [12] Too much of a good thing: immunodeficiency due to hyperactive PI3K signaling.J Clin Invest. 2014 Sep;124(9):3688-90. doi: 10.1172/JCI77198. Epub 2014 Aug 18.
• [13] Conservation and covariance in PH domain sequences: physicochemical profile and information theoretical analysis of XLA-causing mutations in the Btk PH domain.Protein Eng Des Sel. 2004 Mar;17(3):267-76. doi: 10.1093/protein/gzh030. Epub 2004 Apr 13.
• [14] Cellular origins of serum complement receptor type 2 in normal individuals and in hypogammaglobulinaemia.Clin Exp Immunol. 1991 Apr;84(1):16-22. doi: 10.1111/j.1365-2249.1991.tb08117.x.
• [15] Disturbed Transcription of TLRs' Negative Regulators and Cytokines Secretion among TLR4- and 9-Activated PBMCs of Agammaglobulinemic Patients.Immunol Invest. 2019 Nov;48(8):860-874. doi: 10.1080/08820139.2019.1604742. Epub 2019 Jun 11.