A cohort of 314 patients with pheochromocytoma and functional paraganglioma had blood samples collected and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened for mutations. 25 patients had germline VHL mutations, 16 of which had a family history and 9 patients had an apparently sporadic presentation, 11 were male and 14 were female, the median age of diagnosis is 23.9 and range of diagnosis was 4-49. Out of the 25 patients 23 had adrenal tumours, 4 had para-adrenal tumours, and 9 had other VHL lesions (renal tumours and hemangioblastomas). 1 patient with positive family history and/or a syndromic presentation was found with pheochromocytoma or functional paraganglioma and a germline missense VHL mutation (p.L184H (c.551T>A), referred to in the paper by c.608T>A due to a difference in transcript sequence). Other phenotypes unique to the patient are unknown. ACMG: PP4

Among patients prospectively followed by the members of the French VHL Study Group, 35 consecutive patients with well-documented endocrine pancreatic tumour (20 women and 15 men; median age,37 [21Y-57] years) were included. The data from 7 patients with EPT have been partially reported previously in Hammel et al., 1995;2000. All 35 patients had VHL germline mutations and were assessed for the presence of pheochromocytoma and renal carcinoma in addition to pancreatic tumours. The presence of other phenotypes was not described. Patient no. 31 from family 463 had a missense mutation in the VHL gene (c.551T>A) and presented with pancreatic endocrine tumour and pheochromocytoma. The patient's phenotypes are highly specific to VHL disease (PP4) and disease-causing missense variants are common in VHL disease (PP2).