The discovery of the involvement of fibrillin-1 has raised high hopes for a protein or DNA test applicable to MFS patients. Immunofluorescence studies of cultured fibro-blasts and skin sections of patients using monoclonal antibodies against fibrillin have revealed that the amount of fibrillin deposition or fibrillin microfibrils is greatly reduced. Therefore immunofluorescence analysis could be helpful in diagnosis. However, the method has proven to be insufficiently sensitive and specific because of the existence of non-MFS type 1 fibrillinopathies and genetic heterogeneity. Therefore an abnormal test result does not diagnose MFS, and a normal test result does not rule out MFS.
The identification of the FBN1 gene has allowed the development of two types of diagnostic tests: genetic family studies or mutation identification. Family studies can be performed with specific FBN1 polymorphic markers to identify the mutation-bearing haplotype. These studies are only reliable in families in which several affected individuals are available because the involvement of an FBN1 mutation (and not that of another gene) must be clearly demonstrated. However, most family structures do not comply with this requirement. Furthermore, the method is inappropriate in sporadic cases. In practice, these instances represent over 40% of the cases referred for biological diagnosis. The second molecular test is mutation identification. Mutation identification is very costly and long. In effect, there is no quick and 100% reliable method to investigate a large (~ 230 kb) and highly fragmented (10 kb of coding sequence fragmented
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