ArticleAmerican journal of human genetics1997
The molecular basis of partial penetrance of splicing mutations in cystic fibrosis.
Article in American journal of human genetics, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Cystic fibrosis prenatal screening in genetic counseling practice: recommendations of the National Society of Genetic Counselors.Journal of genetic counseling · 2005Guideline
- Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial.The Lancet. Respiratory medicine · 2015Trial
- Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study.Respiratory research · 2005Trial
- The annulus: composition, role and importance in sperm flagellum biogenesis and male fertility.Basic and clinical andrology · 2024Review
- Accurate and Automated Genotyping of theInternational journal of molecular sciences · 2024Article
- All exons are not created equal-exon vulnerability determines the effect of exonic mutations on splicing.Nucleic acids research · 2024Article
- An intronic RNA element modulates Factor VIII exon-16 splicing.Nucleic acids research · 2024Article
- Using the ACMG/AMP framework to capture evidence related to predicted and observed impact on splicing: Recommendations from the ClinGen SVI Splicing Subgroup.American journal of human genetics · 2023Article
- APPLICATION OF THE ACMG/AMP FRAMEWORK TO CAPTURE EVIDENCE RELEVANT TO PREDICTED AND OBSERVED IMPACT ON SPLICING: RECOMMENDATIONS FROM THE CLINGEN SVI SPLICING SUBGROUP.medRxiv : the preprint server for health sciences · 2023Article
- The pathogenic c.1171A>G (p.Arg391Gly) and c.2359G>A (p.Val787Ile) ABCC6 variants display incomplete penetrance causing pseudoxanthoma elasticum in a subset of individuals.Human mutation · 2022Article
- Oligonucleotide-based therapies for cystic fibrosis.Current opinion in pharmacology · 2022Review
- CFTR bearing variant p.Phe312del exhibits function inconsistent with phenotype and negligible response to ivacaftor.JCI insight · 2022Article
- Elucidating clinical phenotypic variability associated with the polyT tract and TG repeats in CFTR.Human mutation · 2021Article
- Antisense oligonucleotide-based drug development for Cystic Fibrosis patients carrying the 3849+10 kb C-to-T splicing mutation.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2021Article
- Accurate, ultra-low coverage genome reconstruction and association studies in Hybrid Swarm mapping populations.G3 (Bethesda, Md.) · 2021Article
- Splicing in the Diagnosis of Rare Disease: Advances and Challenges.Frontiers in genetics · 2021Review
- The intronic BRCA1 c.5407-25T>A variant causing partly skipping of exon 23-a likely pathogenic variant with reduced penetrance?European journal of human genetics : EJHG · 2020Article
- Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells.Nucleic acids research · 2020Article
- Mechanisms of tissue and cell-type specificity in heritable traits and diseases.Nature reviews. Genetics · 2020Review
- Correlating Cystic Fibrosis Transmembrane Conductance Regulator Function with Clinical Features to Inform Precision Treatment of Cystic Fibrosis.American journal of respiratory and critical care medicine · 2019Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The splicing variant, 5T allele, in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene was shown to be associated with partial penetrance of the clinical expression. This splicing variant leads to two possible transcripts: one normal and the other aberrantly spliced that lacks exon 9. The aim of this study was to analyze the molecular basis of the partial penetrance in individuals carrying the 5T allele. We analyzed the level of the correctly spliced RNA transcribed from the 5T allele in nasal and epididymal epithelium and correlated it with disease expression. Semiquantitative nondifferential reverse-transcriptase-PCR showed a considerable variability (6%-37%) in the total level of correctly spliced RNA transcribed from the 5T allele in nasal epithelium from 11 patients. A significant nonlinear correlation (r = .82, P = .002) between the level of the normal CFTR transcripts and the severity of lung disease was shown. No individuals with normal lung function and minimal or no lung disease (FEV1 >80% predicted) had <25% of normal transcripts, and individuals with <15% of normal transcripts did not have FEV1 >80%. The level of normal transcripts in epididymal epithelial cells from four infertile males with congenital bilateral absence of the vas deferens was low (6%-24%). In infertile males with normal lung function the level of correctly spliced transcripts in the nasal epithelium was higher than the level in the epididymal epithelium. These results indicate that there is variability in the efficiency of the splicing mechanism, among different individuals and between different organs of the same individual. This variability provides the molecular basis of the partial penetrance of cystic fibrosis disease in patients carrying the 5T allele.
Indexed as
Identifiers
8981951PMC1712544W1511128892What 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.