Identification and molecular characterization of a de novo supernumerary ring chromosome 18 in a patient with Klippel-Trenaunay syndrome

Abstract

Klippel-Trenaunay syndrome (KTS) is a congenital vascular disorder comprised of capillary, venous and lymphatic malformations associated with overgrowth of the affected tissues. In this study, we report the identification of a de novo supernumerary ring chromosome in a patient with mild mental retardation, long tapering fingers, elongated, thin feet and Klippel-Trenaunay syndrome (KTS). The ring marker chromosome was found to be mosaic, present in 24% of cells, and was later shown to be derived from chromosome 18, r(18). Fluorescence in situ hybridization (FISH) was used to define the breakpoints involved in the formation of r(18). The chromosome 18p breakpoint was localized between the markers WI-9619 and D18S1150, which is less than 10 cM to the centromere. The 18q breakpoint was localized between the centromere and BAC clone 666n19, which is a region of less than 40 kb. These data suggest that the r(18) mostly originated from 18p, with an estimated size of less than 10 cM. These studies identify and characterize a new marker chromosome 18, provide insights into the understanding of the relationships between the clinical phenotypes and marker chromosomes, and establish a framework for finding a potential vascular and/or overgrowth gene located on chromosome 18.