Systematic analysis of splicing defects in selected primary immunodeficiencies-related genes

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Authors

GRODECKÁ Lucie HUJOVÁ Pavla KRAMÁREK Michal KRSJAKOVA Tereza KOVÁČOVÁ Tatiana VONDRÁŠKOVÁ Katarína RAVCUKOVA Barbora HRNČÍŘOVÁ Kristýna SOUČEK Přemysl FREIBERGER Tomáš

Year of publication 2017
Type Article in Periodical
Magazine / Source Clinical Immunology
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://www.sciencedirect.com/science/article/pii/S1521661616305083?via%3Dihub
Doi http://dx.doi.org/10.1016/j.clim.2017.03.010
Field Immunology
Keywords Splicing prediction; Splicing-affecting variants; Cryptic splice sites; Primary immunodeficiencies
Description Both variants affecting splice sites and those in splicing regulatory elements (SREs) can impair pre-mRNA splicing, eventually leading to severe diseases. Despite the availability of many prediction tools, prognosis of splicing affection is not trivial, especially when SREs are involved. Here, we present data on 92 in silico-/55 minigene-analysed variants detected in genes responsible for the primary immunodeficiencies development (namely BTIC, CD4OLG, IL2RG, SERPINGI, STAT3, and WAS). Of 20 splicing-affecting variants, 16 affected splice site while 4 disrupted potential SRE. The presence or absence of splicing defects was confirmed in 30 of 32 blood-derived patients' RNAs. Testing prediction tools performance, splice site disruptions and creations were reliably predicted in contrast to SRE-affecting variants for which just ESRseq, Delta HZ(EI)-scores and EX-SKIP predictions showed promising results. Next, we found an interesting pattern in cryptic splice site predictions. These results might help PID-diagnosticians and geneticists cope with potential splicing-affecting variants. (C) 2017 Elsevier Inc. All rights reserved.
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