FBN2 has been genetically linked to a rare disorder that shares features of Marfan syndrome: congenital contractural arachnodactyly (CCA) (OMIM 120150).The clinical manifestations of CCA are essentially found in the skeleton and associated with distinctive manifestations including crumpled ears and campodactyly.Except for the cardiovascular system, in which Fbn1 gene activity is early and always higher than Fbn2, Fbn2 transcripts appear earlier than Fbn1 transcripts and accumulate for a short period of time just before overt tissue differentiation, i.e., a window of time immediately preceding elastogenesis.In contrast, the amount of Fbn1 transcripts increases at an apparently gradual rate throughout morphogenesis and is mainly expressed during late morphogenesis and well-defined organ structures.Presently no definite genotype/phenotype correlations have been identified except for neonatal mutations (see pathogenic mechanisms).To facilitate their identification, a ‘Marfan database’ has been developed that includes not only molecular but also clinical data.
It may be advantageous to allow some degree of extensibility of assembled microfibrils in tissues subjected to mechanical forces.Several mutations were identified in this gene in CCA patients.The FBNL gene is expressed in many tissues but it is not expressed in brain and lymphocytes.The amino acid sequence of the FBNL gene is 36.3% identical to FBN1 (OMIM 134797) and 35.4% identical to FBN2.
FBNL contains one EGF-like module and five repeated cb EGF-like modules.
The C-terminal domains of the fibrillins are homologous to the C-terminal domain of all four members of the fibulin family, and thus a new type of extracellular module of approximately 120 amino acid residues in length has been proposed. When the FBN1 gene was cloned, a second gene sharing a high degree of homology was identified and located on chromosome 5.