Section 9
Chapter 8,993

Marfan syndrome: fibrillin expression and microfibrillar abnormalities in a family with predominant ocular defects

Kielty, C.M.; Davies, S.J.; Phillips, J.E.; Jones, C.J.; Shuttleworth, C.A.; Charles, S.J.

Journal of Medical Genetics 32(1): 1-6


ISSN/ISBN: 0022-2593
PMID: 7897619
DOI: 10.1136/jmg.32.1.1
Accession: 008992661

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We have found abnormal fibrillin microfibrils isolated from tissues and cell cultures from two cousins with Marfan syndrome whose major clinical abnormality is bilateral ectopia lentis, but who also have skeletal 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 isolated from ciliary zonules and vitreous were highly fragmented when examined by rotary shadowing electron microscopy. Investigation of microfibrils elaborated by patient dermal fibroblasts showed remarkable variations in periodicity and packing. The synthesis and secretion of fibrillin by these cells was confirmed electrophoretically with the identification of metabolically labelled immunoprecipitated fibrillin (M(r) 300,000) in medium and cell layer compartments. These data show that fibrillin expression is normal but that assembled microfibrils are manifestly abnormal both morphologically and functionally. The occurrence of microfibrils with variable periodicities and susceptibility to fragmentation suggests that structural weakness is probably the primary cause of lens dislocation in these patients.

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