Central European Institute of Technology, Masaryk University, Brno, Czech Republic; Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic.
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic.
Clin Immunol. 2017 Jul;180:33-44. doi: 10.1016/j.clim.2017.03.010. Epub 2017 Mar 27.
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, ΔHZ-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.
两种影响剪接位点的变体和那些影响剪接调控元件（SREs）的变体都可能损害前体 mRNA 的剪接，最终导致严重疾病。尽管有许多预测工具可用，但剪接影响的预后并不简单，特别是涉及 SREs 时。在这里，我们提供了 92 个在负责原发性免疫缺陷发展的基因中检测到的（即 BTK、CD40LG、IL2RG、SERPING1、STAT3 和 WAS）在体/55 个小基因分析的变体的数据。在 20 个剪接影响变体中，16 个影响剪接位点，而 4 个破坏潜在的 SRE。在 32 个血液来源患者的 RNA 中，有 30 个证实存在或不存在剪接缺陷。测试预测工具的性能，与影响 SRE 的变体相比，剪接位点的破坏和创建可以可靠地预测，而 ESRseq、ΔHZ 评分和 EX-SKIP 预测只显示出有希望的结果。接下来，我们在隐匿剪接位点预测中发现了一个有趣的模式。这些结果可能有助于 PID 诊断医生和遗传学家应对潜在的剪接影响变体。
