HistoryThis section has been translated automatically.
Knowledge of rare genetic diseases such as hereditary angioedema (HAE) has evolved in parallel with the development of new molecular tools. C1 inhibitor (C1-INH) deficiency has been recognized as the major cause of HAE (HAE-C1-INH) since the 1960s. Discovery of the broad spectrum of mutations affecting the C1-INH gene (SERPING1) was not possible until the late 1980s, when Sanger sequencing became available and more readily accessible worldwide.
However, the involvement of other genes in HAE was not discovered until 2006 with the description of mutations in the F12 gene in patients with HAE and normal C1-INH. The knowledge gained through the new era of genomics has been crucial for the discovery of mutations in additional genes, improving or explaining the understanding of the complex pathogenesis of this phenotypically largely identical disease. In the last three years, advanced next-generation sequencing techniques have enabled the identification of mutations in five additional novel genes associated with hereditary angioedema variants with normal C1-INH (nC1-INH-HAE): ANGPT1 (angiopoietin-1), PLG (plasminogen), KNG1 (kininogen), MYOF (myoferlin), and HS3ST6 (heparan sulfate glucosamine 3-O-sulfotransferase 6).
ClassificationThis section has been translated automatically.
Type I Hereditary angioedema, mutation in Serping1 (C1-INH deficiency)
Type II Hereditary angioedema , mutation in Serping1 (C1-INH dysfunction)
Type III Hereditary angioedema , mutation in factor XII (F12)
Type IV Hereditary angioedema , mutation in plasminogen (PLG)
Type V Hereditary angioedema , mutation in angiopoietin 1 (ANGPT1)
Type VI Hereditary angioedema , mutation in kininogen 1 (KNG1)
Type VII Hereditary angioedema , mutation in myoferlin (MYOF)
Type VIII Hereditary angioedema , mutation in heparan sulfate (HS)-glucosamine 3-O-sulfotransferase 6 (HS3ST6)
Type U Hereditary angioedema, mutation unknown
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EtiopathogenesisThis section has been translated automatically.
Basically, hereditary angioedema can be distinguished between:
- hereditary angioedema with mutation in the C1-esterase inhibitor gene (SERPING1): C1-INH-HAE (HAE type I/ HAE type II)
- hereditary angioedemawithout detectable mutation in SERPING1 gene: nC1-INH-HAE (HAE types III - VIII) with normal C1-INH (see below classification).
Note: Mutations in SERPING1, the gene encoding C1-INH (C1 esterase inhibitor), are responsible for the vast majority of cases of hereditary angioedema. C1-esterase inhibitor (C1-INH) is an important regulator of critical enzymes involved in the cascades of bradykinin formation. These increased vascular permeability and allow the flow of fluids into the extracellular space. Disturbances in this cascade can lead to acute swelling conditions (angioedema).
LocalizationThis section has been translated automatically.
Face, extremities (especially arms, less frequently legs), genitals; also lips, tongue, abdomen (abdominal cramps). Life-threatening: swelling of the larynx.
LiteratureThis section has been translated automatically.
- Santacroce R et al (2021) The genetics of hereditary angioedema: A review. J Clin Med 10: 2023.
- Veronez CL et al (2021) The Expanding Spectrum of Mutations in Hereditary Angioedema. J Allergy Clin Immunol Pract 9: 2229-2234.
Incoming links (13)Ace inhibitor-induced angioedema; Angioedema acquired; Angioedema hereditary 6; Angioedema hereditary type i; Angioedema histamine-mediated; Angioedema of the head and neck region; Complement system; Ecallantide; Edema, hereditary angioedema; Facial swelling; ... Show all
Outgoing links (7)Angioedema hereditary 1; Angioedema Hereditary 3; Angioedema hereditary 4 ; Angioedema hereditary 6; Angioedema hereditary 7; Angioedema hereditary 8; Angiooedema, hereditary, 5;
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