ArticleScientific reports2021
mRNA analysis identifies deep intronic variants causing Alport syndrome and overcomes the problem of negative results of exome sequencing.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Gene-disease relationships for glomerular phenotypes: expert recommendations from ClinGen.Nature reviews. Nephrology · 2026Review
- mRNA Sequencing to Identify Aberrant Splicing in X-linked Alport Syndrome.Kidney international reports · 2026Article
- Systematic reassessment of reported variants in individuals with suspicion of Alport spectrum disorder reveals a high rate of ambiguous results.European journal of human genetics : EJHG · 2026Article
- Update on Alport Syndrome: The Report of the 2024 International Workshop on Alport Syndrome.Kidney international reports · 2026Article
- Whole-genome sequencing identified a deep intronic COL4A5 variant causing aberrant splicing in a female patient with X-linked Alport syndrome.CEN case reports · 2026Article
- Case Report: a novel non-canonical splice site variant in COL4A5 in a patient with Alport syndrome.Frontiers in medicine · 2026Article
- Predisposition of an Intronic Duplication in CHEK2 Gene in the Cases of Breast Cancer from Balochistan.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- A comprehensive splicing characterization of COL4A5 mutations and prognostic significance in a single cohort with X-linked alport syndrome.Frontiers in genetics · 2025Article
- Case Report: Whole genome sequencing identifies a novel deep intronicFrontiers in pediatrics · 2025Article
- Association of Genetically Predicted Skipping of COL4A4 Exon 27 with Hematuria and Albuminuria.Journal of the American Society of Nephrology : JASN · 2025Article
- Noncoding variants are a rare cause of recessive developmental disorders in trans with coding variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis.Kidney international reports · 2023Article
- Article
- Abnormal mRNA Splicing Effect ofKidney international reports · 2023Article
- Intronic position +9 and -9 are potentially splicing sites boundary from intronic variants analysis of whole exome sequencing data.BMC medical genomics · 2023Article
- What patients want to know about genetic testing for kidney disease.Frontiers in medicine · 2023Article
- A woman with Alport syndrome in compound-heterozygous state in pregnancy: lessons for the clinical nephrologist.Journal of nephrology · 2022Article
- From First to Second: How Stickler's Diagnostic Genetics Has Evolved to Match Sequencing Technologies.Genes · 2022Review
- The 2019 and 2021 International Workshops on Alport Syndrome.European journal of human genetics : EJHG · 2022Article
- A Homozygous Deep Intronic Variant Causes Von Willebrand Factor Deficiency and Lack of Endothelial-Specific Secretory Organelles, Weibel-Palade Bodies.International journal of molecular sciences · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in COL4A3, COL4A4 and COL4A5 genes lead to Alport syndrome (AS). However, pathogenic variants in some AS patients are not detected by exome sequencing. The aim of this study was to identify the underlying genetic causes of five unrelated AS probands with negative NGS test results. Urine COL4A3-5 mRNAs were analyzed in the probands with an uncertain inherited mode of AS, and COL4A5 mRNA of skin fibroblasts was analyzed in the probands with X-linked AS. RT-PCR and direct sequencing were performed to detect mRNA abnormalities. PCR and direct sequencing were used to analyze the exons with flanking intronic sequences corresponding to mRNA abnormalities. Six novel deep intronic splicing variants in COL4A4 and COL4A5 genes that cannot be captured by exome sequencing were identified in the four AS probands. Skipping of an exon was caused by an intronic variant, and retention of an intron fragment caused by five variants. In the remaining AS proband, COL4A5 variants c.2677 + 646 C > T and r.2678_r.2767del were detected at the DNA and RNA level, respectively, whereas it is unclear whether c.2677 + 646 C > T may not lead to r.2678_r.2767del. Our results reveal that mRNA analysis for AS genes from either urine or skin fibroblasts can resolve genetic diagnosis in AS patients with negative NGS results. We recommend analyzing COL4A3-5 mRNA from urine as the first choice for these patients because it is feasible and non-invasive.
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