Naslov
Hereditary angioedema due to C1-inhibitor deficiency in south-eastern Europe: SERPING1 mutations and genetic factors modifying the clinical phenotype

Autori
Rijavec, M. ; Košnik, M. ; Zidarn, M. ; Andrejević, S. ; Karadža-Lapić, L. ; Cikojević, D. ; Grivčeva-Panovska, V. ; Korošec, P.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
EUROPEAN JOURNAL OF HUMAN GENETICS / - , 2019, 1360-1361

Skup
52nd Conference of the European Society of Human Genetics (ESHG 2019)

Mjesto i datum
Göteborg, Švedska, 15.06.2019. - 18.06.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
hereditary angioedema ; C1-inhibitor deficiency ; clinical phenotype

Sažetak
Introduction: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare genetic disorder characterized by recurrent oedemas and large heterogeneity in clinical presentation. Our aim was to determine the spectrum of SERPING1 mutations in C1-INH-HAE patients, including genotype-phenotype relationship and if functional genetic variants in F12 and KLKB1 affect the disease expression. Materials and Methods: A cohort of 150 clinically well characterised C1-INH-HAE patients from 75 unrelated families from Croatia, Republic of Macedonia, Serbia, and Slovenia was recruited for genetic analysis, which included sequencing and MLPA analysis of SERPING1, as well as detection of F12 (rs1801020) and KLKB1 (rs3733402) variants. Results: We have identified 39 different mutations (14 missense, 11 nonsense, 7 frameshift, 1 in- frame deletion, 2 splicing defects, 1 substitution affecting the promoter, 3 large indels). Thirteen mutations have not been previously described. When addressing the genotype-phenotype relationship we found that patients with nonsense and frameshift mutations, large indels, splicing defects, and mutations affecting the C1-INH active site (at Arg444) exhibited an increased clinical severity score, compared with those with missense mutations, excluding mutations at Arg444. Importantly, the F12 variant was associated with disease onset. No association between KLKB1 variant and disease expression was identified. Conclusions: Our study identified 39 different, among them 13 novel, disease-causing mutations in C1-INH-HAE patients, highlighting the heterogeneity of mutations in the SERPING1 gene. The mutations with a clear effect on C1-INH function predispose patients to a more severe disease phenotype and the CC F12 variant to earlier disease onset.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA