Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F23%3AN0000070" target="_blank" >RIV/00023728:_____/23:N0000070 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/23:00132410 RIV/00216208:11130/23:10467081 RIV/00216208:11110/23:10467081 RIV/00216208:11140/23:10467081 and 5 more

Result on the web

<a href="https://doi.org/10.1007/s10875-023-01565-w" target="_blank" >https://doi.org/10.1007/s10875-023-01565-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10875-023-01565-w" target="_blank" >10.1007/s10875-023-01565-w</a>

Result language

angličtina

Original language name

Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort

Original language description

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare and life-threatening condition characterized by recurrent localized edema. We conducted a systematic screening of SERPING1 defects in a cohort of 207 Czech patients from 85 families with C1-INH-HAE. Our workflow involved a combined strategy of sequencing extended to UTR and deep intronic regions, advanced in silico prediction tools, and mRNA-based functional assays. This approach allowed us to detect a causal variant in all families except one and to identify a total of 56 different variants, including 5 novel variants that are likely to be causal. We further investigated the functional impact of two splicing variants, namely c.550 + 3A > C and c.686 7C > G using minigene assays and RT-PCR mRNA analysis. Notably, our cohort showed a considerably higher proportion of detected splicing variants compared to other central European populations and the LOVD database. Moreover, our findings revealed a significant association between HAE type 1 missense variants and a delayed HAE onset when compared to null variants. We also observed a significant correlation between the presence of the SERPING1 variant c.-21 T > C in the trans position to causal variants and the frequency of attacks per year, disease onset, as well as Clinical severity score. Overall, our study provides new insights into the genetic landscape of C1-INH-HAE in the Czech population, including the identification of novel variants and a better understanding of genotype-phenotype correlations. Our findings also highlight the importance of comprehensive screening strategies and functional analyses in improving the C1-INH-HAE diagnosis and management.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30102 - Immunology

Project

<a href="/en/project/NV18-05-00330" target="_blank" >NV18-05-00330: Genetic determination of bradykinin-mediated angioedema severity in patients with hereditary angioedema</a><br>

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Clinical Immunology

ISSN

0271-9142

e-ISSN

1573-2592

Volume of the periodical

43

Issue of the periodical within the volume

8

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

18

Pages from-to

1974-1991

UT code for WoS article

001152100100045

EID of the result in the Scopus database

2-s2.0-85168616078