Characterization of von Hippel Lindau gene variants in an African American cohort

Autosomal-dominant (AD) pathogenic/likely pathogenic (P/LP) variants in von Hippel-Lindau (VHL) gene cause VHL disease. We characterize VHL variants and disease phenotypes in Black/African American (AA) patients, a demographic that has not been thoroughly studied. Black/AA patients undergoing germline genetic testing at a CLIA-certified commercial laboratory from November 2014 to March 2022 and carrying a P/LP AD VHL gene variant were identified. Personal and family histories were obtained from test requisition forms, and patients were categorized into VHL disease subtypes: type 1, type 2A, type 2B, and type 2C. Patients with a personal or family history of cancer but no lesions typical of VHL disease were categorized as "unclassified." Patients with an incomplete personal or family history available were noted as "unknown." Final analysis included 38 patients. Among the cohort's personal cancer history, hemangioblastoma and pheochromocytoma were most prevalent (16%). Among the cohort's family cancer history, renal cell carcinoma was most prevalent (8%). Type 1 was the most common VHL disease class recorded (34%). Substitution variants were most common (76%); p.Arg167Trp (c.499C>T) was the most common substitution (8%). Unique variants in Black/AA patients include p.Pro81Leu (c.242C>T), p.Leu129Pro (c.386T>C), p.Asp121Val (c.362A>T), p.His110Profs∗49 (c.329del), and p.Arg82His (c.245G>A). This dataset informs future research on VHL disease and treatment in Black/AA populations.