Systematic analysis of splicing defects in selected primary immunodeficiencies-related genes
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
28359783
DOI
10.1016/j.clim.2017.03.010
PII: S1521-6616(16)30508-3
Knihovny.cz E-resources
- Keywords
- Cryptic splice sites, Primary immunodeficiencies, Splicing prediction, Splicing-affecting variants,
- MeSH
- Hep G2 Cells MeSH
- Child MeSH
- Exons MeSH
- HeLa Cells MeSH
- Complement C1 Inhibitor Protein MeSH
- Infant MeSH
- Complement C1 Inactivator Proteins genetics MeSH
- Humans MeSH
- RNA, Messenger genetics MeSH
- Mutation MeSH
- Child, Preschool MeSH
- Wiskott-Aldrich Syndrome Protein genetics MeSH
- Agammaglobulinaemia Tyrosine Kinase MeSH
- Interleukin Receptor Common gamma Subunit genetics MeSH
- Recombinant Fusion Proteins genetics MeSH
- RNA Splicing * MeSH
- Immunologic Deficiency Syndromes genetics MeSH
- STAT3 Transcription Factor genetics MeSH
- Protein-Tyrosine Kinases genetics MeSH
- U937 Cells MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- BTK protein, human MeSH Browser
- CD40LIg fusion protein MeSH Browser
- IL2RG protein, human MeSH Browser
- Complement C1 Inhibitor Protein MeSH
- Complement C1 Inactivator Proteins MeSH
- RNA, Messenger MeSH
- Wiskott-Aldrich Syndrome Protein MeSH
- Agammaglobulinaemia Tyrosine Kinase MeSH
- Interleukin Receptor Common gamma Subunit MeSH
- Recombinant Fusion Proteins MeSH
- SERPING1 protein, human MeSH Browser
- STAT3 protein, human MeSH Browser
- STAT3 Transcription Factor MeSH
- Protein-Tyrosine Kinases MeSH
- WAS protein, human MeSH Browser
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 BTK, CD40LG, IL2RG, SERPING1, 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, ΔHZEI-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.
References provided by Crossref.org
SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE
Bending of DNA duplexes with mutation motifs
