Hereditary angioedema in a single family with specific mutations in both plasminogen and SERPING1 genes

Abstract

Summary Background Hereditary angioedema (HAE) is a group of genetic diseases characterized by recurrent, painful and potentially lethal tissue swelling. The most common form results from mutations in the SERPING1 gene, leading to reduced function of complement 1 inhibitor (C1‐INH). Rarer forms with normal C1‐INH may arise from mutations in the coagulation factor F12 gene, but mostly the genetic background is unknown. Recently, a novel HAE mutation in the plasminogen (PLG) gene was shown. Patients and methods We analyzed the various clinical manifestations of HAE in 14 related patients using clinical data, biochemical analysis for C1‐INH and C4 as well as gene sequencing. Results Patients’ symptoms were assigned to two different forms of HAE. In ten patients suffering from swelling of the lips or tongue but not of the extremities, a mutation in the PLG gene (c.988A>G) was found whereas in the only four patients with swelling of the gastrointestinal tract and extremities, a mutation in the SERPING1 gene (c.1480C>T) was identified. In two cases this was additional to PLG c.988A>G. Conclusions This unique finding of two different HAE‐specific mutations in a large family not only explains the divergent phenotypes but also supports a genotype‐phenotype correlation showing that abdominal attacks and swelling of the extremities are common with HAE‐C1‐INH but unusual with HAE‐PLG.

Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence

“…In a case series from France, 10 patients were described with a median annual number of attacks of 5 and a median attack duration of 2 days [ 55 ]. OCs, ACE inhibitors, and psychological stress have been observed to trigger or exacerbate attacks in HAE-PLG patients [ 10 , 50 , 51 , 54 – 56 ].…”

“…Thereby, 13 German families with the PLG mutation were identified [10]. Subsequently, more cases of HAE-PLG were identified in various European countries, the United States, and Japan [49][50][51][52][53][54][55][56]. Thus, a total of 146 patients from 33 families were reported (Table 3).…”

Angioedema. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society (PTD) and Polish Society of Allergology (PTA)

“…3) HAE-ANG -with a mutation in the angiopoietin 1 gene, 4) HAE-KNG1 -with a mutation in the kininogen-1 gene, and 5) HAE-UNK -angioedema of unknown origin, where no inducing mutation could be identified [2,6,10,46,47].…”

Angioedema. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society (PTD) and Polish Society of Allergology (PTA)

“…HAE-UNK – angioedema of unknown origin, where no inducing mutation could be identified [ 2 , 6 , 10 , 46 , 47 ].…”