ArticlePediatric nephrology (Berlin, Germany)2017
Functional assessment of a novel COL4A5 splice region variant and immunostaining of plucked hair follicles as an alternative method of diagnosis in X-linked Alport syndrome.
Article in Pediatric nephrology (Berlin, Germany), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 24 citations in OpenAlex.
- mRNA Sequencing to Identify Aberrant Splicing in X-linked Alport Syndrome.Kidney international reports · 2026Article
- Thin Glomerular Basement Membrane Phenotypes With No Identified PathogenicKidney international reports · 2026Article
- Association of Genetically Predicted Skipping of COL4A4 Exon 27 with Hematuria and Albuminuria.Journal of the American Society of Nephrology : JASN · 2025Article
- Aberrant Splicing ofInternational journal of nephrology and renovascular disease · 2024Article
- The NM_033380.2 transcript of theFrontiers in genetics · 2024Article
- Molecular dynamics and minigene assay of new splicing variant c.4298-20T>A ofFrontiers in genetics · 2023Article
- The Contribution ofFrontiers in medicine · 2022Review
- A deep intronic splice variant of theFrontiers in pediatrics · 2022Article
- Identification of Four NovelFrontiers in genetics · 2022Article
- Functional assessment of a novelAnnals of translational medicine · 2021Article
- Determination of the pathogenicity of a novel COL4A5 missense variant by CRISPR-Cas9 in kidney podocytes.American journal of translational research · 2021Article
- Genetic background, recent advances in molecular biology, and development of novel therapy in Alport syndrome.Kidney research and clinical practice · 2020Review
- Pathogenic evaluation of synonymous COL4A5 variants in X-linked Alport syndrome using a minigene assay.Molecular genetics & genomic medicine · 2020Article
- Determination of the pathogenicity of known COL4A5 intronic variants by in vitro splicing assay.Scientific reports · 2019Article
- Expert consensus guidelines for the genetic diagnosis of Alport syndrome.Pediatric nephrology (Berlin, Germany) · 2019Review
- Expert consensus guidelines for the genetic diagnosis of Alport syndrome.Pediatric nephrology (Berlin, Germany) · 2019Review
- Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2018Article
- Functional splicing analysis in an infantile case of atypical hemolytic uremic syndrome caused by digenic mutations in C3 and MCP genes.Journal of human genetics · 2018Article
- Systematic Analysis of Splice-Site-Creating Mutations in Cancer.Cell reports · 2018Article
- An in vitro splicing assay reveals the pathogenicity of a novel intronic variant in ATP6V0A4 for autosomal recessive distal renal tubular acidosis.BMC nephrology · 2017Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMany COL4A5 splice region variants have been described in patients with X-linked Alport syndrome, but few have been confirmed by functional analysis to actually cause defective splicing. We sought to demonstrate that a novel COL4A5 splice region variant in a family with Alport syndrome is pathogenic using functional studies. We also describe an alternative method of diagnosis.
methodsTargeted next-generation sequencing results of an individual with Alport syndrome were analyzed and the results confirmed by Sanger sequencing in family members. A splicing reporter minigene assay was used to examine the variant's effect on splicing in transfected cells. Plucked hair follicles from patients and controls were examined for collagen IV proteins using immunofluorescence microscopy.
resultsA novel splice region mutation in COL4A5, c.1780-6T>G, was identified and segregated with disease in this family. This variant caused frequent skipping of exon 25, resulting in a frameshift and truncation of collagen α5(IV) protein. We also developed and validated a new approach to characterize the expression of collagen α5(IV) protein in the basement membranes of plucked hair follicles. Using this approach we demonstrated reduced collagen α5(IV) protein in affected male and female individuals in this family, supporting frequent failure of normal splicing.
conclusionsDiffering normal to abnormal transcript ratios in affected individuals carrying splice region variants may contribute to variable disease severity observed in Alport families. Examination of plucked hair follicles in suspected X-linked Alport syndrome patients may offer a less invasive alternative method of diagnosis and serve as a pathogenicity test for COL4A5 variants of uncertain significance.
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