Fumarate Hydratase Variants and Their Association With Paraganglioma/Pheochromocytoma

• DOI: 10.1016/j.urology.2022.11.053
• Publication Date: 2023-02-10T01:49:14Z
• Authors: Shirin Zavoshi; Eric Lu; Paul C. Boutros; Liying Zhang; Avital Harari; Kathryn E. Hatchell; Sarah M. Nielsen; Edward D. Esplin; Karen Ouyang; Keith Nykamp; Blake Wilde; Heather Christofk; Brian Shuch
• Keywords: Fumarase

ObjectiveTo clarify the link between germline variants in fumarate hydratase (FH), hereditary leiomyomatosis and renal cell cancer (HLRCC), paraganglioma (PGL) pheochromocytoma (PCC) we utilize a well-annotated testing database.MethodsRecords of 120,061 patients receiving were obtained. FH classified into 4 categories: autosomal dominant (AD) HLRCC variants, recessive (AR) fumarase deficiency (FMRD), previously reported as PGL/PCC unknown significance (VUS) not associated with (NPP-VUS). Rates compared those negative genetic testing.ResultsAbout 1.3% individuals carried which more common among to without (3.1% vs 1.3%, P < .0001). rates higher (22.2% 0.9%, Neither AD (0.3% = .35) nor AR FMRD (1.4% .19) an increased prevalence PGL/PCC. An was detected NPP-VUS (2.0% .0023).ConclusionsCertain confer risk PGL/PCC, but necessarily HLRCC. While universal screening for all does appear warranted, it should be considered select high-risk variants.