24 c.227_229delTCT p.Phe76del p.F76del Sporadic VHL
Between 1994 and 2001, the Dutch VHL working group conducted DNA analysis on 146 probands with VHL-associated manifestations. DNA of probands was extracted from peripheral blood samples. Exons 1, 2 and 3 of the VHL gene and their flanking untranslated and intronic coding sequences were amplified by PCR and subjected to semi-automated sequence analysis. Screening for structural rearrangements, including deletions, involving the VHL gene was performed by Southern blot analysis and the multiplex ligation-dependent probe amplification (MLPA) assay. Deletions encompassing the entire VHL gene were confirmed by FISH analysis on lymphocytes from affected individuals. VHL mutations were identified in 43 families. This in-frame deletion variant (c.227_229delTCT) was detected in 2 VHL families: 24 and 25. Family no. 24 was a type 2 family with 1 patient with central nervous system hemangioblastoma, pheochromocytoma, renal cell carcinoma, and epididymal cysts. They were identified as sporadic with their parents being excluded from having a germline mutation, although they were not available for DNA analysis. Family no.25 had 2 members with retinal hemangioblastomas and renal cell carcinoma, as well as 1 member with CNS hemangioblastoma. This was published in a future publication: PMID: 32179488.