The Genetics of Hereditary Angioedema: A Review
Hereditary angioedema is a rare inherited disorder characterized by recurrent episodes of the accumulation of fluids outside of the blood vessels, causing rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway. Mutations in SERPING1, the gene that encodes C1-INH (C1 e...
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MDPI AG
2021-05-01
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| author | Rosa Santacroce Giovanna D'Andrea Angela Bruna Maffione Maurizio Margaglione Maria d'Apolito |
| author_facet | Rosa Santacroce Giovanna D'Andrea Angela Bruna Maffione Maurizio Margaglione Maria d'Apolito |
| author_sort | Rosa Santacroce |
| collection | DOAJ |
| description | Hereditary angioedema is a rare inherited disorder characterized by recurrent episodes of the accumulation of fluids outside of the blood vessels, causing rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway. Mutations in SERPING1, the gene that encodes C1-INH (C1 esterase inhibitor), are responsible for the majority of cases of hereditary angioedema. C1 esterase inhibitor (C1-INH) is a major regulator of critical enzymes that are implicated in the cascades of bradykinin generation, which increases the vascular permeability and allows the flow of fluids into the extracellular space and results in angioedema. Moreover, a dominantly inherited disease has been described that has a similar clinical picture to C1-INH-HAE (Hereditary angioedema due to C1 inhibitor deficiency), but with normal C1-INH level and activity. This new type of HAE has no mutation in the SERPING1 gene and it is classified as nC1-INH-HAE (HAE with normal C1-INH). Currently mutations in six different genes have been identified as causing nC1-INH-HAE: factor XII (F12), plasminogen (PLG), angiopoietin 1 (ANGPT1), Kininogen 1 (KNG1), Myoferlin (MYOF), and heparan sulfate (HS)-glucosamine 3-O-sulfotransferase 6 (HS3ST6). In this review we aim to summarize the recent advances in genetic characterization of angioedema and possible future prospects in the identification of new genetic defects in HAE. We also provide an overview of diagnostic applications of genetic biomarkers using NGS technologies (<i>Next Generation Sequencing</i>). |
| first_indexed | 2024-03-10T11:35:43Z |
| format | Article |
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| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T11:35:43Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-7ffd4b69a2b64292bd15c5c6d4ee4cc12023-11-21T18:52:56ZengMDPI AGJournal of Clinical Medicine2077-03832021-05-01109202310.3390/jcm10092023The Genetics of Hereditary Angioedema: A ReviewRosa Santacroce0Giovanna D'Andrea1Angela Bruna Maffione2Maurizio Margaglione3Maria d'Apolito4Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyMedical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyHuman Anatomy, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyMedical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyMedical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyHereditary angioedema is a rare inherited disorder characterized by recurrent episodes of the accumulation of fluids outside of the blood vessels, causing rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway. Mutations in SERPING1, the gene that encodes C1-INH (C1 esterase inhibitor), are responsible for the majority of cases of hereditary angioedema. C1 esterase inhibitor (C1-INH) is a major regulator of critical enzymes that are implicated in the cascades of bradykinin generation, which increases the vascular permeability and allows the flow of fluids into the extracellular space and results in angioedema. Moreover, a dominantly inherited disease has been described that has a similar clinical picture to C1-INH-HAE (Hereditary angioedema due to C1 inhibitor deficiency), but with normal C1-INH level and activity. This new type of HAE has no mutation in the SERPING1 gene and it is classified as nC1-INH-HAE (HAE with normal C1-INH). Currently mutations in six different genes have been identified as causing nC1-INH-HAE: factor XII (F12), plasminogen (PLG), angiopoietin 1 (ANGPT1), Kininogen 1 (KNG1), Myoferlin (MYOF), and heparan sulfate (HS)-glucosamine 3-O-sulfotransferase 6 (HS3ST6). In this review we aim to summarize the recent advances in genetic characterization of angioedema and possible future prospects in the identification of new genetic defects in HAE. We also provide an overview of diagnostic applications of genetic biomarkers using NGS technologies (<i>Next Generation Sequencing</i>).https://www.mdpi.com/2077-0383/10/9/2023HAEC1-INH-HAEnC1-INH-HAESERPING1F12PLG |
| spellingShingle | Rosa Santacroce Giovanna D'Andrea Angela Bruna Maffione Maurizio Margaglione Maria d'Apolito The Genetics of Hereditary Angioedema: A Review Journal of Clinical Medicine HAE C1-INH-HAE nC1-INH-HAE SERPING1 F12 PLG |
| title | The Genetics of Hereditary Angioedema: A Review |
| title_full | The Genetics of Hereditary Angioedema: A Review |
| title_fullStr | The Genetics of Hereditary Angioedema: A Review |
| title_full_unstemmed | The Genetics of Hereditary Angioedema: A Review |
| title_short | The Genetics of Hereditary Angioedema: A Review |
| title_sort | genetics of hereditary angioedema a review |
| topic | HAE C1-INH-HAE nC1-INH-HAE SERPING1 F12 PLG |
| url | https://www.mdpi.com/2077-0383/10/9/2023 |
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