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 D197FS (c.589del) was found in a VHL type 1 family with 3 individuals. 1 had retinal angiomas diagnosed at 38Y and 1 with renal cell carcinoma diagnosed at 25Y.