Clinical and Molecular Studies in Families With Congenital or Hereditary Cataracts

Although the etiology of some secondary cataracts is becoming better understood and certain animal models have the promise to elucidate the relationships between lens crystallin and hereditary cataract, little is known about the causes of congenital cataracts in humans. Even the classification of different types of cataracts is cumbersome and imperfect. A better understanding of cataractogenesis will come through an understanding of the molecular components of the lens of the eye and the ways in which lesions of these components are manifested structurally and functionally as opacity of the lens. It is well known that cataracts exhibit marked genetic heterogeneity. In mice and humans, hereditary cataracts have been shown to result from lesions at many distinct loci and those cataracts corresponding to one locus can be morphologically heterogeneous, implying that environmental factors may modify the phenotype of the cataract which a molecular lesion causes. Nonetheless, molecular biological characterization of cataracts in the mouse and guinea pig has suggested that alterations in lens crystallins can cause hereditary cataracts making them reasonable candidate genes for causing hereditary cataracts in humans. In addition, it is apparent that hereditary lesions which mimic or contribute additively to environmental stresses known to cause cataracts might be candidate genes for causing hereditary cataracts. This knowledge increases the feasibility of genetic linkage studies and provides a rationale basis on which to begin the molecular analysis of naturally occurring hereditary cataracts. Therefore, it is the purpose of this protocol to concentrate upon hereditary cataracts.