A Rare Branch-Point Mutation Is Associated with Missplicing of Fibrillin-2 in a Large Family with Congenital Contractural Arachnodactyly

摘要: Summary Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that phenotypically similar to but genetically distinct from Marfan syndrome. Genetic-linkage analysis has implicated the fibrillin-2 gene (FBN2) as CCA locus. Mutation of two isolated patients revealed missense mutations, indicating defects in FBN2 may be responsible for this disorder. However, cosegregation a mutant allele with disease phenotype not yet been established. We have investigated primary cause large well-characterized kindred five generations comprising 18 affected individuals. Previous studies demonstrated linkage family's FBN2. cDNA derived proband and her brother, using nonisotopic RNase cleavage assay, partial skipping exon 31. Approximately 25% transcript produced, which apparently sufficient phenotype. Sequence genomic DNA unusual base composition intron 30 identified mutation, g-26t transversion, vicinity splicing branch-point site 30. Genomic additional family members, both unaffected, then was analyzed mutation. The results clearly demonstrate branchpoint mutation This first report multiplex family, unequivocally establishing mutations are In addition, only very rarely associated human disease, suggesting influences stability.