GUCY2D Gene Mutations in CORD5 Families and Evidence of Incomplete Penetrance

Abstract

Abstract: : Purpose: Positional Cloning of the gene for CORD5 Methods: Recombinant Analysis and Candidate gene Screening Results: The locus for CORD5 an autosomal dominant retinal disease that primarily affects cone function has previously been mapped to human chromosome 17p12-13. One of our "unaffected" recombinant individual from family 1175 was found to cross through the interval between markers D17S926/D17S849 and D17S945/D17S804. Reexamination revealed that he was in fact mildly affected. This expanded the minimum candidate region. Using direct sequencing of the GUCY2D and other candidate genes within this interval, we screened 2 American families affected with CORD5. We identified a R838C missense mutation within the GUCY2D gene in one and a R838H missense mutation in another families. The previously reported mutations for CORD6 are clustered at the same position within this gene. Conclusions: We conclude that GUCY2D mutations cause CORD5, both CORD5 and CORD6 are actually the same disease and significant variability in expression and incomplete penetrance exists even within one family.

Keywords: positional cloning • retinal degenerations: hereditary