Genetic alterations and pathways in patients with Hereditary Angioedema of Unknown Cause (U-HAE)

Objective: Hereditary angioedema ( HAE) with normal C1 inhibitor (HAE-nC1-INH), is a genetically complex, rare disease and mutations in F12, ANGPT1, PLG, MYOF genes are found in some families with HAE-nC1-INH. However, often a specific mutation cannot be identified and this type is called as hereditary angioedema of unknown cause (U-HAE). Our aim was to identify putative causative genetic alterations and/or pathways by whole exome sequencing in patients with U-HAE

Hereditary angioedema

Herediter anjiyoödem, fatal larinks ödemine ve gastrointestinal sistem tıkanıklığına benzeyen bulgulara yol açabilen, tekrarlayıcı anjiyoödem ataklarıyla karakterize, nadir görülen, otozomal dominant geçişli bir hastalıktır. Atakları sıklıkla travma, stres, hormonal tedaviler ve ACE inhibitörleri tetikler. Tanı, C4 ve C1 inhibitör düzeylerindeki düşüklüğün ve C1 inhibitör fonksiyonundaki azalmanın gösterilmesiyle konur. Hastalığın profilaktik tedavisinde atenüe androjenler ve traneksamik asit kullanılır. Akut atakların tedavisinde C1 inhibitör konsantresi infüzyonu tercih edilen tedavi yöntemidir. Bu konuda genetik mühendislik yöntemiyle üretilen C1 inhibitör; kallikrein inhibitörü ve bradikinin reseptör antagonistleriyle ilgili çalışmalar devam etmektedir.Hereditary angioedema is a rare autosomal dominant disease characterized by recurrent episodes of angioedema which can cause fatal laryngeal oedema and features mimicking gastrointestinal tract obstruction. Attacks are usually precipitated by trauma, stress, hormonal therapy and ACE inhibitors The diagnosis is confirmed by the presence of a low serum C4 and reduced C1 inhibitor level or function. Attenuated androgens and tranexamic acid are used for the prophylactic treatment of the disease. C1 inhibitor concentrate infusion is the treatment of choice for acute attacks. There are new products in trial, including genetically engineered C1 esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist