Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed and confirmed that higher risk of pheochromocytoma is associated with missense mutations that result in substitution of a surface amino acid or that disrupt the structural integrity of the VHL gene product (pVHL). Age-related risks of retinal hemangoblastomas and renal cell carcinoma were higher in patients with nonsense or frameshift mutations. Southern blot and/or MLPA analysis by whole blood detected this mutation (c.562delC) was found in 2 family members with renal cell carcinomas, one with retinal angiomas (diagnosed at 25Y), and one with cerebellar hemangioblastoma (diagnosed at 24Y).