Complete molecular analysis of the VHL gene on genomic DNA was conducted on 4 patients and some of their relatives. Peripheral blood lymphocytes were collected and the VHL gene dosage was evaluated by quantitative Southern blot or real-time quantitative PCR analysis. The coding region was studied via direct sequencing. One patient (4), a 16 year old female, was found to harbour a polymorphic variant on the 3' UTR of the VHL gene (c.*1149 A>G). This patient also harboured the promoter region mutation c.–65_–55dup11 of the VHL gene. She presented with an isolated retinal angioma and an unremarkable family history although the dup11 variant was inherited from an nonsymptomatic parent. ACMG evidence codes: 'PP4' since the patient presents phenotypes highly specific for a disease with a single genetic etiology.

PatientID: 4

KindredID: 4

Case: F, 16Y0M, Ethnicity Unknown

DiseaseAssertion: retinal capillary hemangioma

FamilyInfo: N/A - family history was unremarkable. The paper states however that this patient inherited the duplication from a nonsymptomatic parent.

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: a 16- year-old girl referred to this center for VHL testing due to an isolated retinal angioma

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.*1149A>G

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2573130264 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2573130264

gnomAD: N/A

VariantEvidence: Quantitative Southern blot/real-time quantitative PCR analyses was normal in this patient. Known polymorphic variant on the 3’UTR of the VHL gene, as well as the 5’UTR. PCR–RFLP assay approach showed that both alleles were expressed in apparently equimolar amounts (Fig. 2d) suggesting that the 11 bp duplication has no effect on expression of the affected allele.

MutationType: 3_prime_UTR_variant

CivicName: c.–65_–55dup11 AND 3' UTR alteration (c.*1149A>G)

MultipleGeneVariants: Germline, VHL, c.–65_–55dup11