Familial occurrence of typical and severe lethal congenital contractural arachnodactyly caused by missplicing of exon 34 of fibrillin-2

Mei Wang, Carol L. Clericuzio, Maurice Godfrey

Research output: Contribution to journalArticle

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Abstract

Genetic linkage studies have linked congenital contractural arachnodactyly (CCA), a usually mild heritable connective-tissue disorder, to FBN2, the fibrillin gene on chromosome 5. Recently, FBN2 mutations in two patients with CCA have been described. Here we report an A→T transversion at the -2 position of the consensus acceptor splice site, resulting in the missplicing of exon 34, a calcium-binding epidermal growth factor-like repeat in fibrillin-2 in a mother and daughter with CCA. Significantly, the mother exhibited a classic CCA phenotype with arachnodactyly, joint contractures, and abnormal pinnae, whereas her daughter exhibited a markedly more severe CCA phenotype, which included cardiovascular and gastrointestinal anomalies that led to death in infancy. Analysis of cloned fibroblasts showed that the mother is a somatic mosaic for the exon 34 missplicing mutation, whereas all the daughter's cells harbored the mutation.

Original languageEnglish (US)
Pages (from-to)1027-1034
Number of pages8
JournalAmerican Journal of Human Genetics
Volume59
Issue number5
StatePublished - Oct 29 1996

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Exons
Nuclear Family
Mothers
Mutation
Arachnodactyly
Phenotype
Chromosomes, Human, Pair 5
RNA Splice Sites
Genetic Linkage
Contracture
Epidermal Growth Factor
Connective Tissue
Fibroblasts
Joints
Fibrillin-2
Congenital contractural arachnodactyly
Calcium
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Familial occurrence of typical and severe lethal congenital contractural arachnodactyly caused by missplicing of exon 34 of fibrillin-2. / Wang, Mei; Clericuzio, Carol L.; Godfrey, Maurice.

In: American Journal of Human Genetics, Vol. 59, No. 5, 29.10.1996, p. 1027-1034.

Research output: Contribution to journalArticle

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