Congenital Contractural Arachnodactyly (CCA), also known as Beal's syndrome, is an autosomal dominant disorder characterized by multiple congenital joint contractures, arachnodactyly, dolichostenomelia, and scoliosis with only rare ocular or cardiovascular involvement. CCA has been linked to the fibrillin-2 (FBN2) gene located on chromosome 5q23-31. The phenotype ofCCA is similar to Marfan syndrome (MFS) which is caused by defects in the fibrillin-1 (FBNl) gene located on chromosome 15. Fibrillin-1 and fibrillin-2 are components of extracellular matrix (ECM) elastic microfibrils. The linkage studies performed on families affected with CCA suggest that another gene in the area ofFBN2 could also be responsible for CCA. Microfibril associated protein-3 (MF AP-3), another microfibril protein gene, has been localized to chromosome 5q32-33.2, the region of FBN2. This study involves mutation analysis of five patients affected with CCA, three of whom are representative of families affected with CCA. Mutation analysis was performed by chemical mismatch cleavage (CMC) analysis and nonisotopic RNase cleavage assay (NIRCA) analysis on both FBN2 and MF AP-3 cDNA. Prior to this study only two mutations in FBN2 have been reported in two isolated patients with CCA and none have been reported for MFAP-3. The two mutations reported in FBN2 have not been confirmed in other affected family members. Mutation analysis by CMC completed in this study did not reveal any mutations in either FBN2 or MF AP-3. Reanalysis by NIRCA revealed two mutations in FBN2. One mutation which results in the skipping of exon 31 occurs in an intron and its location is presently unknown. The other mutation, a G to C transversion at nucleotide 3340, predicting a histidine substitution for an asparagine, is a mutation at the -1 position of the 5' splice site of an intron which results in partial exon skipping although it is unknown whether exon 25 or 26 is skipped. The missense mutation and partial exon skipping result in two different forms of mutant fibrillin-2 molecules. Both of the mutations are present in patients with additional affected family members. Characterization of these mutations will confirm the cosegregation of FBN2 mutations with the CCA phenotype.
| Identifer | oai:union.ndltd.org:pdx.edu/oai:pdxscholar.library.pdx.edu:open_access_etds-6269 |
| Date | 01 May 1996 |
| Creators | Babcock, Darcie |
| Publisher | PDXScholar |
| Source Sets | Portland State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Dissertations and Theses |
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