MARFAN-SYNDROME - FIBRILLIN EXPRESSION AND MICROFIBRILLAR ABNORMALITIES IN A FAMILY WITH PREDOMINANT OCULAR DEFECTS

We have found abnormal fibrillin microfibrils isolated from tissues an d cell cultures from two cousins with Marfan syndrome whose major clin ical abnormality is bilateral ectopia lentis, but who also have skelet al involvement but no cardiovascular defects. Ultrastructural analysis of ciliary zonules showed the presence of abundant loose microfibril bundles which in many places appeared disorganised. Microfibrils isola ted from ciliary zonules and vitreous were highly fragmented when exam ined by rotary shadowing electron microscopy. Investigation of microfi brils elaborated by patient dermal fibroblasts showed remarkable varia tions in periodicity and packing. The synthesis and secretion of fibri llin by these cells was confirmed electrophoretically with the identif ication of metabolically labelled immunoprecipitated fibrillin (M(r) 3 00 000) in medium and cell layer compartments. These data show that fi brillin expression is normal but that assembled microfibrils are manif estly abnormal both morphologically and functionally. The occurrence o f microfibrils with variable periodicities and susceptibility to fragm entation suggests that structural weakness is probably the primary cau se of lens dislocation in these patients.