Comprehensive characterization of Alu‐mediated breakpoints in germline VHL gene deletions and rearrangements in patients from 71 VHL families
| Autor: | Christopher J. Ricketts, Berton Zbar, Laura S. Schmidt, W. Marston Linehan, Cathy D. Vocke, Mark W. Ball, Lindsay A. Middelton |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
von Hippel-Lindau Disease von Hippel‐Lindau Alu repeat Alu element Biology urologic and male genital diseases Germline 03 medical and health sciences Exon VHL Genetics medicine Vhl gene Humans In patient germline deletion Genetics (clinical) Research Articles Germ-Line Mutation 030304 developmental biology hereditary renal cell carcinoma 0303 health sciences 030305 genetics & heredity Breakpoint Cancer medicine.disease medicine.anatomical_structure Germ Cells genomic rearrangement Von Hippel-Lindau Tumor Suppressor Protein Female Pancreas Gene Deletion Research Article |
| Zdroj: | Human Mutation |
| ISSN: | 1098-1004 1059-7794 |
| Popis: | 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 this study, we have extensively characterized germline deletions identified in patients from 71 VHL families managed at the National Cancer Institute, including 59 partial (PD) and 12 complete VHL deletions (CD). Deletions that ranged in size from 1.09 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. Von Hippel‐Lindau (VHL) is a hereditary multisystem disorder caused by germline alterations in the VHL gene. This study characterized 59 partial and 12 complete VHL germline deletions in 71 VHL families ranging in size from 1.09 to 355 kb. Exact breakpoints were mapped for 55 partial and 3 complete germline deletions and 95% involved Alu repeats at both breakpoints, with a common “hotspot” pair of Alu repeats observed in 12 families. |
| Databáze: | OpenAIRE |
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