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CONTEXT: Von Hippel-Lindau (VHL) disease manifests as a variety of benign and malignant neoplasms. Previous studies of VHL disease have documented several genotype-phenotype correlations; however, many such correlations are still unknown. Increased identification of new mutations and patients with previously described mutations will allow us to better understand how VHL mutations influence disease phenotypes.

PATIENTS AND DESIGN: A total of 45 individuals from five unrelated families were evaluated, of which 21 patients were either diagnosed with VHL disease or showed strong evidence related to this disease. We compared the patients' gene sequencing results with their medical records including computed tomography or magnetic resonance imaging scans, eye examinations, and laboratory/pathological examinations. Patients were also interviewed to obtain information regarding their family history.

RESULTS: We identified four missense mutations: c. 239G>T (p.Ser80Ile), linked with VHL Type 2B, was associated with renal cell carcinoma (RCC), pheochromocytoma (Pheo), and hemangioma (HB) in the cerebellum; c. 232A>T (p.Asn78Tyr) manifested as RCC alone and likely caused VHL Type 1; c.500G>A (p.Arg167Gln) mutation was more likely to cause VHL Type 2 than Type 1 as it preferentially induced Pheo and HB in the retina, cerebellum, and spinal cord; c.293A>G (p.Try98Cys) was associated with Pheo and thus likely induced VHL Type 2.

CONCLUSIONS: Characterizing VHL disease genotype-phenotype correlations can enhance the ability to predict the risk of individual patients developing different VHL-related phenotypes. Ultimately, such insight will improve the diagnostics, surveillance, and treatment of VHL patients.

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Endocrine Connections

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This article was published in Enocrine Connections.

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Copyright © 2018 The Authors. CC BY NC 4.0