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Cited by 657RNA Research and SplicingGenomics and Rare DiseasesRNA regulation and disease

Splicing mutations in human genetic disorders: Examples, detection, and confirmation

Open access
Anna, Abramowicz, Monika, Gos·2018·Journal of Applied Genetics
DOI 10.1007/s13353-018-0444-7PMC PMC6060985
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Abstract

Precise pre-mRNA splicing, essential for appropriate protein translation, depends on the presence of consensus “cis” sequences that define exon-intron boundaries and regulatory sequences recognized by splicing machinery. Point mutations at these consensus sequences can cause improper exon and intron recognition and may result in the formation of an aberrant transcript of the mutated gene. The splicing mutation may occur in both introns and exons and disrupt existing splice sites or splicing regulatory sequences (intronic and exonic splicing silencers and enhancers), create new ones, or activate the cryptic ones. Usually such mutations result in errors during the splicing process and may lead to improper intron removal and thus cause alterations of the open reading frame. Recent research has underlined the abundance and importance of splicing mutations in the etiology of inherited diseases. The application of modern techniques allowed to identify synonymous and nonsynonymous variants as well as deep intronic mutations that affected pre-mRNA splicing. The bioinformatic algorithms can be applied as a tool to assess the possible effect of the identified changes. However, it should be underlined that the results of such tests are only predictive, and the exact effect of the specific mutation should be verified in functional studies. This article summarizes the current knowledge about the “splicing mutations” and methods that help to identify such changes in clinical diagnosis.

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  • NCSS variants are less straightforward to interpret because they exhibit considerable sequence variation and can easily be missed during genomic DNA analyses.

    “Non-CSS (NCSS) variants are less straightforward to interpret because they exhibit considerable sequence variation and can easily be missed during genomic DNA analyses [43].”

    From Identification of a Novel Non-Canonical Splice-Site Variant in ABCD1 (2023) · cites this paper as [43]

    The Summary (page not available) says splicing mutations outside canonical sites can be missed during genomic DNA analysis. The section on branch points and polypyrimidine tracts (page not available) says their degenerate consensus sequences make variants hard to interpret, but it establishes that sequence-variation point for those motifs rather than for NCSS variants as a whole. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Anna, A., & Monika, G.
ORCID
Monika, Gos
Venue
Journal of Applied Genetics
Publisher
Springer Science and Business Media LLC
Published
2018-04-21
Volume
59
Issue
3
Pages
253-268
ISSN
  • 1234-1983 (ISSN-L)
  • 2190-3883
DOI
10.1007/s13353-018-0444-7
PMC
PMC6060985
OpenAlex
W2799812275
Cited by
657
References
3
Citations by year
2026: 68 · 2025: 76 · 2024: 91 · 2023: 78 · 2022: 101 · 2021: 119 · 2020: 81 · 2019: 37 · 2018: 5
FWCI
5.96
Type
journal article
Language
en
Update notices
correction (2019-03-19)
Open access
Licence
Locations
  • Journal of Applied Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Institute of Mother and Child Intramural Grants
  • Polish National Science Centre (UMO-2013/09/B/NZ2/03164)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
splicing mutation, pre-mRNA splicing, splice site mutation, deep intronic mutation, cryptic splice site, exonic splicing enhancers, exonic splicing silencer, exon-intron boundaries, genetic disorders, variant effect prediction, diagnosis
MeSH terms
Algorithms, Computer Simulation, DNA Mutational Analysis, Exons, Humans, Introns, Mutation, Pyrimidine Nucleotides, RNA Splicing, Point Mutation, Computational Biology, RNA Splice Sites, Genetic Diseases, Inborn

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Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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