Objective: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic syndrome predisposing tocentral nervous system hemangioblastoma (CNS), pheochromocytoma (PCC), renal cell carcinoma(RCC), retinalhemangioma (RA) and renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor gene. Toassess VHL genotype-phenotype correlations with function of pVHL a gene mutation analysis of members ina Chinese family with non-syndromic PCCs and individuals with apparently sporadic pheochromocytoma(ASP) was performed. Materials and
Methods: DNA samples of 20 members from the Chinese family with nonsyndromicPCCs and 41 patients with ASP were analyzed by polymerase chain reaction and direct sequencing,confirmed by Taqman probe.
Results: Three novel mutations (H125P, 623(TTTTGTtG) and R120T) wereidentified in the Chinese family and in 3 among 41 ASP patients. The mutations were all located in exon 2 ofVHL gene encoding β-domain of pVHL. The tumor type in H125P carriers and R120T carriers was VHL type2C. And 623(TTTTGTtG) carriers presented VHL type 2B or type 2C.
Conclusions: VHL gene abnormalitieswere identified in the Chinese family with non-syndromic PCCs and patients with APS, resulting in dysfunctionof pVHL. H125P and R120T could be associated with VHL type 2C, while 623(TTTTGTtG) might be linked withVHL type 2B or type 2C. Not only is the genetic analysis helpful for early diagnosis and treatment of patientswith VHLD, it is also benefitial for research intoVHLD pathogenesis.