Hereditary angioedema with a mutation in the plasminogen gene

K Bork, K Wulff, L Steinmüller‐Magin, I Braenne… - Allergy, 2018 - Wiley Online Library
K Bork, K Wulff, L Steinmüller‐Magin, I Braenne, P Staubach‐Renz, G Witzke, J Hardt
Allergy, 2018Wiley Online Library
Background Hereditary angioedema (HAE) with normal C1‐INH (HAEnCI) may be linked to
specific mutations in the coagulation factor 12 (FXII) gene (HAE‐FXII) or functional mutations
in other genes that are still unknown. We sought to identify and characterize a hitherto
unknown type of HAE with normal C1‐INH and without mutation in the F12 gene. Methods
The study comprised analysis of whole‐exome sequencing, Sanger sequencing, and
clinical data of patients. Results We detected a mutation in the plasminogen (PLG) gene in …
Background
Hereditary angioedema (HAE) with normal C1‐INH (HAEnCI) may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE‐FXII) or functional mutations in other genes that are still unknown. We sought to identify and characterize a hitherto unknown type of HAE with normal C1‐INH and without mutation in the F12 gene.
Methods
The study comprised analysis of whole‐exome sequencing, Sanger sequencing, and clinical data of patients.
Results
We detected a mutation in the plasminogen (PLG) gene in patients with HAEnCI. The mutation c.9886A>G was located in exon 9 leading to the missense mutation p.Lys330Glu (K330E) in the kringle 3 domain of the PLG protein. The mutation was identified by next‐generation sequencing in 14 patients with HAEnCI belonging to 4 of 7 families. Family studies revealed that this type of HAE was transmitted as an autosomal dominant trait. The PLG gene mutation was present in all studied symptomatic patients and was also found in 9 of 38 index patients from 38 further families with HAEnCI. Most patients had swelling of face/lips (78.3%) and tongue (78.3%). A total of 331 of all 3.795 tongue swellings (8.7%) were associated with dyspnea, voice changes, and imminent asphyxiation. Two women died by asphyxiation due to a tongue swelling.
Conclusions
Hereditary angioedema with a mutation in the PLG gene is a novel type of HAE. It is associated with a high risk of tongue swellings.
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