Table 1

Clinical manifestation of 20 consecutive families with von Hippel-Lindau disease (VHL). Details of germline mutations found in VHL families without (type 1) and with (type 2) phaeochromocytoma

VHL FamilyVHL typeFamily historyNoHBRARCPCPHMutation at nt level of ORFfExonConsequence to pVHLfType of mutationReference
aFurther investigation showed that the mother of the patient was an asymptomatic carrier of the mutation. bOne patient per family with renal tumour <3 cm under follow up detected by imaging. cAlthough we did not observe RC, the germline mutations are described as associated with the VHL type 2B phenotype. dPancreatic cystadenoma. eThe proband presented with one tumour which biopsy showed to be a non-functional paraganglioma. fNomenclature according to Antonarakis et al (1998). gProtein stops at residue 142. hProtein stops at residue 157. iNew at nucleotide level, but already described at aa level. jAllele frequency in normal Brazilian population.
No = number of affected members in each VHL family; HB = haemangioblastoma of CNS; RA = retinal angioma; RC = renal carcinoma; PC = pancreatic carcinoma; PH = phaeochromocytoma; nt = nucleotide; ORF = open reading frame; aa = amino acid; new site = novel germline mutation.
11Yes542226-228 del TCT1delPhe76In frame del 41
41Yes323280G>T1Glu94StopNonsense 12
51Yes22302T>G1Leu101ArgMissesnse 31
61No111d305 del C1Frameshift at aa 102gFrameshiftNovel
71Yes5432e320G>C1Arg107ProMissense 33
81Yes22IVS1+7G>AIntron 1Splicing defectNovel
91Yes3111344 del A2Frameshift at aa 115hFrameshiftNovel
121Yes8712b407T>C2Phe136SerMissense 12
131Noa1111b436 del C2Frameshift at aa 146hFrameshiftNovel
141Yes5311dIVS2+1G>AIntron 2Splicing defect 32
152Yes21c2499C>T3Arg167TrpMissense 12
162Yes42c3500G>A3Arg167GlnMissense 12
171Yes101015bPartial deletionRearrangement
181Yes521dPartial deletionRearrangement
191Yes33Partial deletionRearrangement
201Yes643b1Complete deletionRearrangement
9, 17183C>G1SynonymPolymorphism1.16%j
16IVS2 –95T>AIntron 2Apparently no effectPolymorphism1.69%j