Nina Rupar (Avtor), Julij Gyula Šelb (Avtor), Mitja Košnik (Avtor), Mihaela Zidarn (Avtor), Slađana Andrejević (Avtor), Ljerka Čulav (Avtor), Vesna Grivčeva-Panovska (Avtor), Peter Korošec (Avtor), Matija Rijavec (Avtor)

Povzetek

Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is a rare genetic disorder caused by pathogenic variants in the SERPING1 gene and characterised by swelling and a highly variable clinical phenotype. We aimed to identify novel modifying genetic factors predisposing to the clinical symptoms. We performed whole exome sequencing (WES) and comprehensive bioinformatic analysis in symptomatic and asymptomatic (three duos) family members with HAE-C1-INH. Selected variants identified using WES (present in all asymptomatic and absent in symptomatic patients) were determined using Sanger sequencing. We included 88 clinically well-characterised HAE-C1-INH patients from south-eastern Europe (nine asymptomatic) from 42 unrelated families. We identified 39 variants in 23 genes (ANKRD36C, ARGFX, CC2D2B, IL5RA, IRF2BP2, LGR6, MRPL45, MUC3A, NPIPA1, NRG1, OR5M1, OR5M3, OR5M10, OR8U3, PLCL1, PRSS3, PSKH2, PTPRA, RTP4, SEZ6, SLC25A5, VWA3A, and ZNF790). We selected variants in CC2D2B and PLCL1, which were analysed using Sanger sequencing in the entire group of HAE-C1-INH. We found significant differences in the frequencies of the CC2D2B c.190A>G (rs17383738) variant between symptomatic and asymptomatic patients, where heterozygotes were more common in asymptomatic HAE-C1-INH patients in comparison to symptomatic patients (55 % vs 23%; P = 0.049, OR = 4.24, 95% CI 1.07-14.69). Our study identified novel genetic factors that modify the clinical variability of HAE-C1-INH. We further demonstrated, in a large cohort, the importance of the CC2D2B gene as a disease-modifying factor. Based on linkage disequilibrium analysis, the CCNJ and ZNF518A genes might also be involved in the clinical variability of HAE-C1-INH.

Ključne besede

hereditarni angioedem;pomanjkanje zaviralca C1;geni modifikatorji;klinični fenotip;povezave genotip-fenotip;genetska varianta;SERPING1;CC2D2B;hereditary angioedema;C1 inhibitor deficiency;genetic modifiers;clinical phenotype;genotype-phenotype correlation;genetic variant;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL MF - Medicinska fakulteta
UDK: 66
COBISS: 194844163 Povezava se bo odprla v novem oknu
ISSN: 1879-0038
Št. ogledov: 45
Št. prenosov: 29
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: hereditarni angioedem;pomanjkanje zaviralca C1;geni modifikatorji;klinični fenotip;povezave genotip-fenotip;genetska varianta;SERPING1;CC2D2B;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-11
Letnik: ǂVol. ǂ919
Zvezek: [article no.] 148496
Čas izdaje: 2024
DOI: 10.1016/j.gene.2024.148496
ID: 23715898
Priporočena dela:
, ni podatka o podnaslovu
, clinical characteristics, novel SERPING1 mutations, and genetic factors modifying the clinical phenotype
, ǂa ǂclose relationship with C1-INH-HAE
, first national study, diagnostic and prophylactic challenges
, ni podatka o podnaslovu