A NOVEL MUTATION OF THE FIBRILLIN GENE CAUSING ECTOPIA LENTIS

Ectopia lentis (EL), a dominantly inherited connective tissue disorder , has been genetically linked to the fibrillin gene on chromosome 15 ( FBN1) in earlier studies. Here, we report the first EL mutation in the FBN1 gene confirming that EL is caused by mutations of this gene. So far, several mutations in the FBN1 gene have been reported in patients with Marfan syndrome (MFS). EL and MFS are clinically related but dis tinct conditions with typical manifestations in the ocular and skeleta l systems, the fundamental difference between them being the absence o f cardiovascular involvement in EL. We report a point mutation, cosegr egating with the disease in the described family, that displays EL ove r four generations. The mutation changes a conserved glutamic acid res idue in an EGF-like motif, which is the major structural component of the fibrillin and is repeated throughout the polypeptide. In vitro mut agenetic studies have demonstrated the necessity of an analogous gluta mic acid residue for calcium binding in an EGF-like repeat of human fa ctor IX. This provides a possible explanation for the role of this mut ation in the disease pathogenesis. (C) 1994 Academic Press, Inc.