Summary. As part of an attempt to locate the vonHippel-Lindau locus (VHL) on chromosome 3, we evaluated 41 families with yon Hippel-Lindau disease from the United States and Canada. One large family was identified whose disease phenotype was distinct from typical VHL. The most common disease manifestation was pheochromocytoma occuring in 57% (27/47) of affected family members. Few (4/47) affected family members had symptomatic spinal or cerebellar hemangioblastomas; no affected family member had renal cell carcinoma (0/47) or pancreatic cysts (0/24). Previously, genetic analysis demonstrated that the disease manifestations in this family were linked to RAF1 and D3S18, markers shown to be linked to typical VHL. These results suggest that there are mutant alleles at the VHL locus associated with distinct tissue specificities.

The tumors of patients with HPRC pose some diagnostic difficulties because they can be missed by US, are small, and enhance poorly on CT. CT is preferable to US as a screening tool because of its higher sensitivity in detecting small lesions, and when contrast media cannot be administered, MR is a suitable alternative to CT.

Source/Description: XLIB17-11 is a 1.7 kb EcoRI fragment isolated from a Charon 21A human chromosome 3 library (1). Polymorphism: MspI digestion of genomic DNA and hybridization with the probe detects a two-allele polymorphism: 6.0 kb (Al) and 5.0 kb (A2). Frequency: Estimated from 120 unrelated Caucasians A1 :0.47 A2:0.53 Frequency of Heterozygosity: 0.5.

Source/Description: XLIB 13-67 is a 4.3 kb EcoRI fragment isolated from a Charon 21A human chromosome 3 library (1). Polymorphism: MspI digestion of genomic DNA and hybridization with the probe detects a two-allele polymorphism: 20.0 kb (Al) and 10.0 kb (A2). Frequency: Estimated from 120 unrelated Caucasians A1 :0.25 A2:0.75 Frequency of Heterozygosity: 0.38.