ArticleAmerican journal of human genetics1997
A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.
Article in American journal of human genetics, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 74 citations in OpenAlex.
- MASQ: A multiplex qPCR platform for quantitative alternative splicing analysis in clinical specimens.Molecular therapy. Nucleic acids · 2026Article
- The Fibrillin-1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells.Cancer communications (London, England) · 2022Article
- Variant filtering, digenic variants, and other challenges in clinical sequencing: a lesson from fibrillinopathies.Clinical genetics · 2020Article
- A Novel Splicing Mutation in theFrontiers in genetics · 2020Article
- Activation of cryptic splice sites in three patients with chronic granulomatous disease.Molecular genetics & genomic medicine · 2019Article
- Pathogenicity and selective constraint on variation near splice sites.Genome research · 2019Article
- A novelClinical case reports · 2018Article
- High-Throughput Assays to Assess the Functional Impact of Genetic Variants: A Road Towards Genomic-Driven Medicine.Clinical and translational science · 2017Review
- Article
- RNA-Binding Proteins: Splicing Factors and Disease.Biomolecules · 2015Review
- A novel FBN2 mutation in a Chinese family with congenital contractural arachnodactyly.FEBS open bio · 2015Article
- Ocular phenotype of Fbn2-null mice.Investigative ophthalmology & visual science · 2013Article
- The missing puzzle piece: splicing mutations.International journal of clinical and experimental pathology · 2013Review
- Human Splicing Finder: an online bioinformatics tool to predict splicing signals.Nucleic acids research · 2009Article
- Human branch point consensus sequence is yUnAy.Nucleic acids research · 2008Article
- The molecular genetics of Marfan syndrome and related disorders.Journal of medical genetics · 2006Review
- A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa.American journal of human genetics · 2002Article
- Article
- The molecular genetics of Marfan syndrome and related microfibrillopathies.Journal of medical genetics · 2000Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to but genetically distinct from Marfan syndrome. Genetic-linkage analysis has implicated the fibrillin-2 gene (FBN2) as the CCA locus. Mutation analysis of two isolated CCA patients revealed missense mutations, indicating that defects in FBN2 may be responsible for this disorder. However, cosegregation of a mutant allele with the disease phenotype has not yet been established. We have investigated the primary cause of CCA in a large well-characterized kindred with five generations comprising 18 affected individuals. Previous studies demonstrated linkage of this family's CCA phenotype to FBN2. Mutation analysis of cDNA derived from the proband and her affected brother, using a nonisotopic RNase cleavage assay, revealed the partial skipping of exon 31. Approximately 25% mutant transcript is produced, which is apparently sufficient to cause a CCA phenotype. Sequence analysis of genomic DNA revealed an unusual base composition for intron 30 and identified the mutation, a g-26t transversion, in the vicinity of the splicing branch-point site in intron 30. Genomic DNA from 30 additional family members, both affected and unaffected, then was analyzed for the mutation. The results clearly demonstrate cosegregation of the branch-point mutation with the CCA phenotype. This is the first report of a CCA mutation in a multiplex family, unequivocally establishing that mutation in FBN2 are responsible for the CCA phenotype. In addition, branch-point mutations only very rarely have been associated with human disease, suggesting that the unusual composition of this intron influences splicing stability.
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