Genetics Studies On Hereditary Cataract And Age Related Cataract

In spite of the high incidence of autosomal dominant cataract(ADC) in the Chinese population, there are, however, no reports about linkage analyses of ADC in Chinese families. Here, we identified and analysed a five-generation family affected with lamellar cataract. On the basis of the previous results that a whole genome scan strategy was used to map the disease locus and a linkage was found between markers on 16q22 and the cataract phenotype and previous reports about another congenital cataract locus [Marner cataract (CAM) is located near this region. In 1949, Maner descrided the CAM phenotype in a large Danish family, with 542 member in 8 generations. In1988, Eiberg found that CAM shows strong linkage to haptoglobin], Mutation screening of the heat shock transcription factor 4 gene (HSF4) in this candidate region identified a T to C transition in exon 3, resulting in a Leu115Pro substitution within the DNA-binding domain in the Chinese five-generation family. Furthermore, we identified a C to T transition at nucleotide 362 in affected family members in the Danish family with the Marner's cataract phenotype and two further missense mutations in sporadic cataract cases, resulting in an Ala20Asp and an Ile87Val substitution. These mutations are all within the DNA-binding domain. This work demonstrates that HSF4 is very important in lens development. It is the first report of mutations in a transcription factor regulating heat shock proteins associated with cataract.HSF4 gene regulates HSPs expression. HSPs play an important role in the maintenance of the supramolecular organization of the lens proteins. It has been reported that small heat shock protein (sHSP) functions abnormally in the age related cataract. Changes in HSF4 gene sequence may induce an...