Hereditary angioedema due to C1-inhibitor deficiency in Macedonia

clinical characteristics, novel SERPING1 mutations, and genetic factors modifying the clinical phenotype

Vesna Grivčeva-Panovska (Avtor), Mitja Košnik (Avtor), Peter Korošec (Avtor), Slađana Andrejević (Avtor), Ljerka Karadža-Lapić (Avtor), Matija Rijavec (Avtor)

Povzetek

Objective: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease, characterized by swellings. We aimed to characterize on a clinical and molecular basis C1-INH-HAE patients in the Republic of Macedonia. Results: All 15 patients from six unrelated families were diagnosed with C1-INHHAE type I, with a mean age of symptom onset of 11 years and an average delay of diagnosis of 7 years. Patients reported on average 31 angioedema attacks/year, with a median clinical severity score (CSS) of 7. We identified three known mutations, and two mutations (c.813_818delCAACAA and c.1488T>G) were reported for the first time. To address the genotype-phenotype association, a pooled analysis including 78 C1-INH-HAE south-eastern European patients was performed, with additional analysis of F12-46C/T and KLKB1- 428G/A polymorphisms. We demonstrated that patients with nonsense and frameshift mutations, large deletions/insertions, splicing defects, and mutations at Arg444 exhibited an increased CSS compared with missense mutations, excluding mutations at Arg444. In addition, the CC F12-46C/T polymorphism was suggestive of earlier disease onset. Discussion: Genetic analysis helped identify the molecular basis of C1-INH-HAE given that causative mutations in SERPING1 were detected in all patients, including an infant before the appearance of clinical symptoms. We identified two novel mutations and further corroborated the genotype-phenotype relationship, wherein mutations with a clear effect on C1-INH function predispose patients to a more severe disease phenotype and CC F12-46C/T predisposes patients to earlier disease onset.

Ključne besede

C1 inhibitor;C1-inhibitor deficiency;SERPING1 gene;

Podatki

Jezik:	Angleški jezik
Leto izida:	2018
Tipologija:	1.01 - Izvirni znanstveni članek
Založnik:	Taylor & Francis
UDK:	616-097
COBISS:	2048261745
ISSN:	1365-2060
Št. ogledov:	786
Št. prenosov:	149
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarne ključne besede:	zaviralec C1;pomanjkanje zaviralca C1;gen SERPING1;Angioedemas, hereditary;Genetics;Macedonia;Hereditarni angioedemi;Genetika;Makedonija;
Komentar vira:	Soavtorji: Mitja Košnik, Peter Korošec, Slađana Andrejević, Ljerka Karadža-Lapić, Matija Rijavec; Nasl. z nasl. zaslona; Opis vira z dne 19. 3. 2018;
Strani:	str. 269-276
Letnik:	ǂVol. ǂ50
Zvezek:	ǂiss. ǂ3
Čas izdaje:	2018
DOI:	10.1080/07853890.2018.1449959
ID:	12204572