Genetics of Congenital Cataract-Microcornea Syndrome. (360G-Wellcome-090224_Z_09_Z)

This proposal aims to identify new genes and proteins involved in eye development by studying a cohort of consanguineous families with recessively inherited microcornea, cataract and iris coloboma. This combination of signs and inheritance pattern has not been reported before, though similar conditions have been described. Preliminary analysis showed that two of these families map to new genetic loci on chromosomes 10 and 20 while a third has a mutation in a gene only previously implicated in ca taract alone. I now propose to complete the genetic analysis of the remaining families, screen known genes where they are implicated by the genetics and look for mutations in new eye development genes at the new loci. Initially I will prioritise positional candidate genes then sequence them directly, but if necessary I will use Next Generation sequencing to generate a complete list of all sequence variants within one of the loci to ensure I find the gene involved. Once I have found such a gene I will use the techniques of molecular and cellular biology to characterise it further in order to better understand how the eye develops and how mutations in this gene cause an inherited developmental defect.