Congenital hereditary cataracts

Abstract

Congenital cataracts are rare and occur in developed countries with a frequency of 30 cases among 100,000 births with a further 10 cases being diagnosed during childhood. They reflect mainly genetically caused developmental alterations in the lens and surrounding ocular tissues. Even if modern Human Genetics has made large steps forward in the characterization of human hereditary disorders, the underlying developmental processes can only be investigated in model organisms. The mouse is such a good model because of its similarity (as a mammal) and its genetic characterization. This review brings together our genetic and developmental knowledge of congenital, human cataracts with the corresponding mouse models. First, early events will be influenced by genes coding for transcription factors like Pax6, Pitx3, Maf or Sox. If the lens is maturing, mutations affecting the lens membranes (aquaporins/Mip, Lim-2 or connexins) or the structural proteins of the cytosol of the lens fiber cells (the crystallins) become more important. From a genetic point of view it becomes obvious that cataract-causing mutations are not distributed randomly. The discovery of a broad variety of genes important for eye and lens development made much progress in the recent years. Nevertheless, there still remains a long list of mutations to be characterized and functionally investigated both in mouse and man indicating a broad genetic heterogeneity in that which clinicians simply refer to as a "cataract".