In a study of 426 unrelated VHL patients, 111 were discovered to have alterations in the VHL gene. 18 novel variants were identified in VHL patients, but none were present in 200 unaffected control individuals. DNA samples from peripheral blood leukocytes underwent polymerase chain reaction (PCR) amplification, denaturing high-performance liquid chromatography (DHPLC), and direct sequence analysis of the entire coding sequence and intron-exon boundaries. Mutation G93C (c.277G>T) was identified in proband 43. Proband 43 presented with retinal capillary hemangioma and pheochromocytoma. Proband and mother were found to carry the V84L (c.250G>C) germline mutation of the VHL gene. No phenotype data was provided for the mother.

PatientID: AII2

KindredID: A

Case: F, 33Y0M, Serbian

DiseaseAssertion: VHL

FamilyInfo: Families were selected based on their clinical data and family history. Patient’s mother (AI1) had CNS hemangioblastoma. The patient’s son (AIII3) had severe arterial hypertension since 12Y0M and left pheochromocytoma was found and removed at 24Y0M. The patient’s sister (AII2) has pheochromocytoma and CNS hemangioblastoma. Genetic testing was performed on nine family members and two carried the heterozygous missense variant - current patient and her son. The patient’s mother and sister with VHL were not genetically tested. See pedigree in figure 1.

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: Patient was diagnosed with pheochromocytoma at 33Y0M.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G93C (c.277G>T)

LegacyVariant: p.G93C (c.490G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 223175, https://www.ncbi.nlm.nih.gov/clinvar/variation/223175/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense variant; transversion

CivicName: G93C (c.277G>T)

MultipleGeneVariants: N/A