ArticleAmerican journal of human genetics2019
Pathogenic Abnormal Splicing Due to Intronic Deletions that Induce Biophysical Space Constraint for Spliceosome Assembly.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Long-read DNA and RNA sequencing for inherited polyposis and colorectal cancer: cryptic intronic variants and multiple mutational mechanisms.Journal of medical genetics · 2025Article
- Data-driven insights to inform splice-altering variant assessment.American journal of human genetics · 2025Article
- Refining clinically relevant parameters for mis-splicing risk in shortened introns with donor-to-branchpoint space constraint.European journal of human genetics : EJHG · 2024Article
- Genome and RNA sequencing boost neuromuscular diagnoses to 62% from 34% with exome sequencing alone.Annals of clinical and translational neurology · 2024Article
- Article
- Atypical splicing variants in PKD1 explain most undiagnosed typical familial ADPKD.NPJ genomic medicine · 2023Article
- Introme accurately predicts the impact of coding and noncoding variants on gene splicing, with clinical applications.Genome biology · 2023Article
- SpliceVault predicts the precise nature of variant-associated mis-splicing.Nature genetics · 2023Article
- Biallelic loss-of-function variants in EXOC6B are associated with impaired primary ciliogenesis and cause spondylo-epi-metaphyseal dysplasia with joint laxity type 3.Human mutation · 2022Review
- Centers for Mendelian Genomics: A decade of facilitating gene discovery.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Review
- Empirical prediction of variant-activated cryptic splice donors using population-based RNA-Seq data.Nature communications · 2022Article
- Deep clinicopathological phenotyping identifies a previously unrecognized pathogenic EMD splice variant.Annals of clinical and translational neurology · 2021Article
- What's Wrong in a Jump? Prediction and Validation of Splice Site Variants.Methods and protocols · 2021Review
- Deletion of a pseudogene within a fragile site triggers the oncogenic expression of the mitotic CCSER1 gene.Life science alliance · 2021Article
- Article
- WGS and RNA Studies Diagnose NoncodingNeurology. Genetics · 2021Article
- Machine Learning Approaches for the Prioritization of Genomic Variants Impacting Pre-mRNA Splicing.Cells · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 10 institutions in 3 countries.
Funding
Abstract
A precise genetic diagnosis is the single most important step for families with genetic disorders to enable personalized and preventative medicine. In addition to genetic variants in coding regions (exons) that can change a protein sequence, abnormal pre-mRNA splicing can be devastating for the encoded protein, inducing a frameshift or in-frame deletion/insertion of multiple residues. Non-coding variants that disrupt splicing are extremely challenging to identify. Stemming from an initial clinical discovery in two index Australian families, we define 25 families with genetic disorders caused by a class of pathogenic non-coding splice variant due to intronic deletions. These pathogenic intronic deletions spare all consensus splice motifs, though they critically shorten the minimal distance between the 5' splice-site (5'SS) and branchpoint. The mechanistic basis for abnormal splicing is due to biophysical constraint precluding U1/U2 spliceosome assembly, which stalls in A-complexes (that bridge the 5'SS and branchpoint). Substitution of deleted nucleotides with non-specific sequences restores spliceosome assembly and normal splicing, arguing against loss of an intronic element as the primary causal basis. Incremental lengthening of 5'SS-branchpoint length in our index EMD case subject defines 45-47 nt as the critical elongation enabling (inefficient) spliceosome assembly for EMD intron 5. The 5'SS-branchpoint space constraint mechanism, not currently factored by genomic informatics pipelines, is relevant to diagnosis and precision medicine across the breadth of Mendelian disorders and cancer genomics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.