Cloning and characterization of the breakpoint regions of a chromosome 11;18 translocation in a patient with hamartoma of the retinal pigment epithelium

Mutations of various tumor suppressor genes, e.g., PTEN, TSC1, and TSC2, ar e known to be responsible for different inherited diseases presenting with multiple hamartomas, a benign tumor resembling neoplasia that results from faulty organ development. Combined hamartoma of the retinal pigment epithel ium (RPE) and retina is a rare, congenital, focal malformation of the fundu s. So far, no disease gene has been associated with this disorder. By molec ular analysis of an apparently balanced and reciprocal translocation betwee n the short arms of chromosomes 11 and 18, t(11; 18)(p13;p11.31), in a pati ent with hamartoma of the RPE and retina, we selected PAC clones crossing t he breakpoints on both derivative chromosomes 11 and 18. For the overlappin g chromosome 11 clone, two EST clusters were identified, suggesting the exi stence of at least two genes in the breakpoint region. We constructed a PAC contig and showed that at least three exons of a novel gene map to the bre akpoint region on chromosome 18. Based on the results of FISH analysis with the PAC clones of this contig, we suggest the occurrence of a complex rear rangement. Copyright (C) 2001 S. Karger AG, Basel.