| GROMBIŘÍKOVÁ, Hana, Viktor BÍLY, Přemysl SOUČEK, Michal KRAMÁREK, Roman HAKL, Lucie BALLONOVÁ, Barbora RAVCUKOVA, Dita RICNA, Karolína KOŽENÁ, Lucie KRATOCHVÍLOVÁ, Marta SOBOTKOVA, Radana ZACHOVA, Pavel KUKLÍNEK, Pavlina KRALICKOVA, Irena KRCMOVA, Jana HANZLIKOVA, Martina VACHOVA, Olga KRYSTUFKOVA, Eva DANKOVA, Milos JESENAK, Martina NOVACKOVA, Michal SVOBODA, Jiří LITZMAN and Tomáš FREIBERGER. Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort. Journal of Clinical Immunology. NEW YORK: SPRINGER, 2023, vol. 43, No 8, p. 1974-1991. ISSN 0271-9142. Available from: https://dx.doi.org/10.1007/s10875-023-01565-w. |
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@article{2345961,
author = {Grombiříková, Hana and Bíly, Viktor and Souček, Přemysl and Kramárek, Michal and Hakl, Roman and Ballonová, Lucie and Ravcukova, Barbora and Ricna, Dita and Kožená, Karolína and Kratochvílová, Lucie and Sobotkova, Marta and Zachova, Radana and Kuklínek, Pavel and Kralickova, Pavlina and Krcmova, Irena and Hanzlikova, Jana and Vachova, Martina and Krystufkova, Olga and Dankova, Eva and Jesenak, Milos and Novackova, Martina and Svoboda, Michal and Litzman, Jiří and Freiberger, Tomáš},
article_location = {NEW YORK},
article_number = {8},
doi = {http://dx.doi.org/10.1007/s10875-023-01565-w},
keywords = {HAE; C1-INH-HAE; hereditary angioedema; SERPING1; splicing genotype–phenotype relationship; time to diagnosis},
language = {eng},
issn = {0271-9142},
journal = {Journal of Clinical Immunology},
title = {Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort},
url = {https://link.springer.com/article/10.1007/s10875-023-01565-w},
volume = {43},
year = {2023}
}
TY - JOUR
ID - 2345961
AU - Grombiříková, Hana - Bíly, Viktor - Souček, Přemysl - Kramárek, Michal - Hakl, Roman - Ballonová, Lucie - Ravcukova, Barbora - Ricna, Dita - Kožená, Karolína - Kratochvílová, Lucie - Sobotkova, Marta - Zachova, Radana - Kuklínek, Pavel - Kralickova, Pavlina - Krcmova, Irena - Hanzlikova, Jana - Vachova, Martina - Krystufkova, Olga - Dankova, Eva - Jesenak, Milos - Novackova, Martina - Svoboda, Michal - Litzman, Jiří - Freiberger, Tomáš
PY - 2023
TI - Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort
JF - Journal of Clinical Immunology
VL - 43
IS - 8
SP - 1974-1991
EP - 1974-1991
PB - SPRINGER
SN - 02719142
KW - HAE
KW - C1-INH-HAE
KW - hereditary angioedema
KW - SERPING1
KW - splicing genotype–phenotype relationship
KW - time to diagnosis
UR - https://link.springer.com/article/10.1007/s10875-023-01565-w
N2 - 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.
ER -
GROMBIŘÍKOVÁ, Hana, Viktor BÍLY, Přemysl SOUČEK, Michal KRAMÁREK, Roman HAKL, Lucie BALLONOVÁ, Barbora RAVCUKOVA, Dita RICNA, Karolína KOŽENÁ, Lucie KRATOCHVÍLOVÁ, Marta SOBOTKOVA, Radana ZACHOVA, Pavel KUKLÍNEK, Pavlina KRALICKOVA, Irena KRCMOVA, Jana HANZLIKOVA, Martina VACHOVA, Olga KRYSTUFKOVA, Eva DANKOVA, Milos JESENAK, Martina NOVACKOVA, Michal SVOBODA, Jiří LITZMAN and Tomáš FREIBERGER. Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort. \textit{Journal of Clinical Immunology}. NEW YORK: SPRINGER, 2023, vol.~43, No~8, p.~1974-1991. ISSN~0271-9142. Available from: https://dx.doi.org/10.1007/s10875-023-01565-w.
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