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Clin Transl Allergy. 2019 Feb 14;9:9. doi: 10.1186/s13601-019-0247-x. eCollection 2019.

Identification of the recently described plasminogen gene mutation p.Lys330Glu in a family from Northern Germany with hereditary angioedema.

Author information

1
1Department of Dermatology, Allergology and Venereology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
2
2Division of Clinical and Molecular Allergology, Priority Research Area Asthma and Allergy, Research Center Borstel, Borstel (Sülfeld), Germany.
3
3Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel (Sülfeld), Germany.
4
4Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Lübeck, Lübeck, Germany.
5
Institute of Laboratory Medicine and Human Genetics, Singen, Germany.
6
6Institute of Human Genetics, University of Göttingen, Göttingen, Germany.
7
7Institute of Human Genetics, University of Lübeck, 23538 Lübeck, Germany.
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Contributed equally

Abstract

Hereditary angioedema (HAE) is a life-threatening disease characterized by recurrent episodes of subcutaneous and mucosal swellings and abdominal cramping. Corticosteroids and antihistamines, which are usually beneficial in histamine-induced acquired angioedema, are not effective in HAE. Therefore, diagnosing HAE correctly is crucial for affected patients. We report a family from Northern Germany with six individuals suffering from recurrent swellings, indicating HAE. Laboratory tests and genetic diagnostics of the genes SERPING1, encoding C1 esterase inhibitor (C1-INH), and F12, encoding coagulation factor XII, were unremarkable. In three affected and one yet unaffected member of the family, we were then able to identify the c.988A > G (also termed c.1100A > G) mutation in the plasminogen (PLG) gene, which has recently been described in several families with HAE. This mutation leads to a missense mutation with an amino acid exchange p.Lys330Glu in the kringle 3 domain of plasminogen. There was no direct relationship between the earlier described cases with this mutation and the family we report here. In all affected members of the family, the symptoms manifested in adulthood, with swellings of the face, tongue and larynx, including a fatal case of a 19 year-old female individual. The frequency of the attacks was variable, ranging between once per year to once a month. In one individual, we also found decreased serum levels of plasminogen as well as coagulation factor XII. As previously reported in patients with PLG defects, icatibant proved to be very effective in controlling acute attacks, indicating an involvement of bradykinin in the pathogenesis.

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