Familial occurrence of typical and severe lethal congenital contractural arachnodactyly caused by missplicing of exon 34 of fibrillin-2.
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.
Munroe Center for Human Genetics, University of Nebraska Medical Center, Omaha 68198-5430, USA.
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Wang
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Clericuzio
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Godfrey
D000328:Adult; D003240:Connective Tissue Diseases / Q000151:congenital / Q000235:genetics* / Q000378:metabolism; D003286:Contracture / Q000151:congenital / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D000071840:Fibrillin-2; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy
C000605723:FBN2 protein, human; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins