ArticleBMC medical genetics2001
Multi-exon deletions of the FBN1 gene in Marfan syndrome.
Article in BMC medical genetics, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 63 citations in OpenAlex.
- A Novel Heterozygous Intronic FBN1 Variant Contributes to Aberrant RNA Splicing in Marfan Syndrome.Molecular genetics & genomic medicine · 2024Article
- Correlation between large FBN1 deletions and severe cardiovascular phenotype in Marfan syndrome: Analysis of two novel cases and analytical review of the literature.Molecular genetics & genomic medicine · 2023Review
- The fibrillinopathies: New insights with focus on the paradigm of opposing phenotypes for both FBN1 and FBN2.Human mutation · 2022Review
- Genotype-phenotype correlations of marfan syndrome and related fibrillinopathies: Phenomenon and molecular relevance.Frontiers in genetics · 2022Review
- Proof-of-Concept: Antisense Oligonucleotide Mediated Skipping of Fibrillin-1 Exon 52.International journal of molecular sciences · 2021Article
- A novel splicing mutation in Marfan syndrome.International journal of legal medicine · 2020Article
- Two Novel PathogenicGlobal medical genetics · 2020Article
- Identification of gross deletions in FBN1 gene by MLPA.Human genomics · 2018Article
- Intragenic multi-exon deletion in the FBN1 gene in a child with mildly dilated aortic sinus: a retrotransposal event.Journal of human genetics · 2017Article
- The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative FBN1 mutations.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2016Article
- Review
- A Case Based Approach to Clinical Genetics of Thoracic Aortic Aneurysm/Dissection.BioMed research international · 2016Review
- Qualitative and quantitative analysis of FBN1 mRNA from 16 patients with Marfan Syndrome.BMC medical genetics · 2015Article
- Correlations between long inverted repeat (LIR) features, deletion size and distance from breakpoint in human gross gene deletions.Scientific reports · 2015Article
- Skeletogenic phenotype of human Marfan embryonic stem cells faithfully phenocopied by patient-specific induced-pluripotent stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Characterization of large genomic deletions in the FBN1 gene using multiplex ligation-dependent probe amplification.BMC medical genetics · 2011Article
- Heterozygous mutations of FREM1 are associated with an increased risk of isolated metopic craniosynostosis in humans and mice.PLoS genetics · 2011Article
- The clinical spectrum of complete FBN1 allele deletions.European journal of human genetics : EJHG · 2011Article
- Clinical utility gene card for: Marfan syndrome type 1 and related phenotypes [FBN1].European journal of human genetics : EJHG · 2010Article
- A Marfan syndrome gene expression phenotype in cultured skin fibroblasts.BMC genomics · 2007Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in the fibrillin -1 gene (FBN1) cause Marfan syndrome (MFS), an autosomal dominant multi-system connective tissue disorder. The 200 different mutations reported in the 235 kb, 65 exon-containing gene include only one family with a genomic multi-exon deletion.
methodsWe used long-range RT-PCR for mutation detection and long-range genomic PCR and DNA sequencing for identification of deletion breakpoints, allele-specific transcript analyses to determine stability of the mutant RNA, and pulse-chase studies to quantitate fibrillin synthesis and extracellular matrix deposition in cultured fibroblasts. Southern blots of genomic DNA were probed with three overlapping fragments covering the FBN1 coding exons
resultsTwo novel multi-exon FBN1 deletions were discovered. Identical nucleotide pentamers were found at or near the intronic breakpoints. In a Case with classic MFS, an in-frame deletion of exons 42 and 43 removed the C-terminal 24 amino acids of the 5th LTBP (8-cysteine) domain and the adjacent 25th calcium-binding EGF-like (6-cysteine) domain. The mutant mRNA was stable, but fibrillin synthesis and matrix deposition were significantly reduced. A Case with severe childhood-onset MFS has a de novo deletion of exons 44-46 that removed three EGF-like domains. Fibrillin protein synthesis was normal, but matrix deposition was strikingly reduced. No genomic rearrangements were detected by Southern analysis of 18 unrelated MFS samples negative for FBN1 mutation screening.
conclusionsTwo novel deletion cases expand knowledge of mutational mechanisms and genotype/phenotype correlations of fibrillinopathies. Deletions or mutations affecting an LTBP domain may result in unstable mutant protein cleavage products that interfere with microfibril assembly.
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