ArticlePloS one2011
A novel splice variant in the N-propeptide of COL5A1 causes an EDS phenotype with severe kyphoscoliosis and eye involvement.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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20 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Pooled it
- Next-Generation Sequencing and Variant Analysis of Fibrillar (Pro)Collagens.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Splicing QTL mapping in stimulated macrophages associates low-usage splice junctions with immune-mediated disease risk.Nature communications · 2025Article
- Splicing Analysis of Exonic TSC1 and TSC2 Gene Variants Causing Tuberous Sclerosis Complex.Human mutation · 2025Article
- The Association of a Single Nucleotide Variant inMedicina (Kaunas, Lithuania) · 2024Article
- Donor Splice Site Variant inMedicina (Kaunas, Lithuania) · 2022Article
- Benchmarking deep learning splice prediction tools using functional splice assays.Human mutation · 2021Article
- Article
- Generation of pathogenic TPP1 mutations in human stem cells as a model for neuronal ceroid lipofuscinosis type 2 disease.Stem cell research · 2021Article
- An allele of rs619586 polymorphism in MALAT1 alters the invasiveness of meningioma via modulating the expression of collagen type V alpha (COL5A1).Journal of cellular and molecular medicine · 2020Article
- Systematic analysis of dark and camouflaged genes reveals disease-relevant genes hiding in plain sight.Genome biology · 2019Article
- New variants inPostepy dermatologii i alergologii · 2019Article
- Splicing mutations in human genetic disorders: examples, detection, and confirmation.Journal of applied genetics · 2018Review
- Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium.Human molecular genetics · 2015Article
- Changes in type II procollagen isoform expression during chondrogenesis by disruption of an alternative 5' splice site within Col2a1 exon 2.Matrix biology : journal of the International Society for Matrix Biology · 2014Article
- Molecular properties and fibril ultrastructure of types II and XI collagens in cartilage of mice expressing exclusively the α1(IIA) collagen isoform.Matrix biology : journal of the International Society for Matrix Biology · 2014Article
- Clinical and molecular characterization of 40 patients with classic Ehlers-Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations.Orphanet journal of rare diseases · 2013Article
- Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders.Arquivos brasileiros de endocrinologia e metabologia · 2012Article
- Severe conjunctivochalasis in association with classic type Ehlers-Danlos syndrome.BMC ophthalmology · 2012Article
- Genetic and mechanistic evaluation for the mixed-field agglutination in B3 blood type with IVS3+5G>A ABO gene mutation.PloS one · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Ehlers-Danlos Syndrome (EDS) is a heritable connective tissue disorder characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. The classic subtype of EDS is caused by mutations in one of the type V collagen genes (COL5A1 and COL5A2). Most mutations affect the type V collagen helical domain and lead to a diminished or structurally abnormal type V collagen protein. Remarkably, only two mutations were reported to affect the extended, highly conserved N-propeptide domain, which plays an important role in the regulation of the heterotypic collagen fibril diameter. We identified a novel COL5A1 N-propeptide mutation, resulting in an unusual but severe classic EDS phenotype and a remarkable splicing outcome. METHODOLOGY/PRINCIPAL
findingsWe identified a novel COL5A1 N-propeptide acceptor-splice site mutation (IVS6-2A>G, NM_000093.3_c.925-2A>G) in a patient with cutaneous features of EDS, severe progressive scoliosis and eye involvement. Two mutant transcripts were identified, one with an exon 7 skip and one in which exon 7 and the upstream exon 6 are deleted. Both transcripts are expressed and secreted into the extracellular matrix, where they can participate in and perturb collagen fibrillogenesis, as illustrated by the presence of dermal collagen cauliflowers. Determination of the order of intron removal and computational analysis showed that simultaneous skipping of exons 6 and 7 is due to the combined effect of delayed splicing of intron 7, altered pre-mRNA secondary structure, low splice site strength and possibly disturbed binding of splicing factors. CONCLUSIONS/SIGNIFICANCE: We report a novel COL5A1 N-propeptide acceptor-splice site mutation in intron 6, which not only affects splicing of the adjacent exon 7, but also causes a splicing error of the upstream exon 6. Our findings add further insights into the COL5A1 splicing order and show for the first time that a single COL5A1 acceptor-splice site mutation can perturb splicing of the upstream exon.
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