Von Hippel-Lindau (VHL) is a hereditary multisystem disorder caused by germline alterations in the VHL gene. VHL patients are at risk for benign as well as malignant lesions in multiple organs including kidney, adrenal, pancreas, the central nervous system, retina, endolymphatic sac of the ear, epididymis and broad ligament. An estimated 30-35% of all families with VHL inherit a germline deletion of one, two, or all three exons. In the current study, we have extensively characterized germline deletions identified in patients from 71 VHL families managed at the Deletions ranged in size from 1.09 kb to 355 kb. Fifty-eight deletions (55 PD and 3 CD) have been mapped to the exact breakpoints. Ninety-five percent (55 of 58) of mapped deletions involve Alu repeats at both breakpoints. Several novel classes of deletions were identified in this cohort, including two cases that have complex rearrangements involving both deletion and inversion, two cases with inserted extra Alu-like sequences, six cases that involve breakpoints in Alu repeats situated in opposite orientations, and a “hotspot” PD of exon 3 observed in 12 families that involves the same pair of Alu repeats. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.