ArticleAmerican journal of human genetics2004
Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway.
Article in American journal of human genetics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 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
- Molecular drivers of osteogenesis imperfecta: a cellular and extracellular collagen disease.Clinical science (London, England : 1979) · 2025Review
- Evaluating variants of uncertain significance in adult zebrafish via prime editing: a proof of concept with a COL1A2 variant.BMC medical genomics · 2025Article
- Embryological Divergence and Molecular Mechanisms in Thoracic and Abdominal Aortic Aneurysms: Bridging Developmental Biology and Clinical Insights.Biomolecules · 2025Review
- Exploring skeletal disorders in cattle and sheep: a WGS-based framework for diagnosis and classification.Genetics, selection, evolution : GSE · 2025Article
- Cardiac health, type I collagen, and aging in theAmerican journal of physiology. Heart and circulatory physiology · 2025Article
- Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Genetic diagnosis of the Ehlers-Danlos syndromes.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2024Article
- scRNA-seq reveals the diversity of the developing cardiac cell lineage and molecular players in heart rhythm regulation.iScience · 2024Article
- Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm.International journal of molecular sciences · 2024Review
- To Repair or Replace the Mitral Valve in Ehlers-Danlos Syndrome? A Case Report.The journal of Tehran Heart Center · 2023Article
- Identification and development of the novel 7-genes diagnostic signature by integrating multi cohorts based on osteoarthritis.Hereditas · 2022Article
- Ehlers-Danlos syndromes and their manifestations in the visual system.Frontiers in medicine · 2022Review
- Mutational Screening of Skeletal Genes in 14 Chinese Children with Osteogenesis Imperfecta Using Targeted Sequencing.Journal of immunology research · 2022Article
- Hypermobile Ehlers-Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Review
- Morphological and mechanical characterization of bone phenotypes in the Amish G610C murine model of osteogenesis imperfecta.PloS one · 2021Article
- Loeys-Dietz Syndrome.Advances in experimental medicine and biology · 2021Article
- Analysis of Pathogenic Pseudoexons Reveals Novel Mechanisms Driving Cryptic Splicing.Frontiers in genetics · 2021Article
- Exome Sequencing Reveals a Phenotype Modifying Variant in ZNF528 in Primary Osteoporosis With a COL1A2 Deletion.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Mechanisms of procollagen and HSP47 sorting during ER-to-Golgi trafficking.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Splice site mutations in the COL1A2 gene of type I collagen can give rise to forms of Ehlers-Danlos syndrome (EDS) because of partial or complete skipping of exon 6, as well as to mild, moderate, or lethal forms of osteogenesis imperfecta as a consequence of skipping of other exons. We identified three unrelated individuals with a rare recessively inherited form of EDS (characterized by joint hypermobility, skin hyperextensibility, and cardiac valvular defects); in two of them, COL1A2 messenger RNA (mRNA) instability results from compound heterozygosity for splice site mutations in the COL1A2 gene, and, in the third, it results from homozygosity for a nonsense codon. The splice site mutations led to use of cryptic splice donor sites, creation of a downstream premature termination codon, and extremely unstable mRNA. In the wild-type allele, the two introns (IVS11 and IVS24) in which these mutations occurred were usually spliced slowly in relation to their respective immediate upstream introns. In the mutant alleles, the upstream intron was removed, so that exon skipping could not occur. In the context of the mutation in IVS24, computer-generated folding of a short stretch of mRNA surrounding the mutation site demonstrated realignment of the relationships between the donor and acceptor sites that could facilitate use of a cryptic donor site. These findings suggest that the order of intron removal is an important variable in prediction of mutation outcome at splice sites and that folding of the nascent mRNA could be one element that contributes to determination of order of splicing. The complete absence of pro alpha 2(I) chains has the surprising effect of producing cardiac valvular disease without bone involvement.
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.