The proband’s son (III.1) inherited his father’s germline VHL large deletion, and not the VHL p. Pro81Ser variant. In addition, the son (III.1) was found to have a hemizygous VHL c.340 + 5 G→C (IVS1 + 5) polymorphic variant, present on the allele inherited from his healthy mother (II.2). The son (III.1) was, therefore, clinically screened and found to have retinal and cerebellar hemangioblastomas as well as pancreatic cysts, typical lesions of VHL demonstrating that VHL cosegregated with, and is therefore caused by, the VHL large deletion and not the p.Pro81Ser variant.
PatientID: III.1
KindredID: 3
Case: M, Age Unknown, Ethnicity Unknown
DiseaseAssertion: VHL
FamilyInfo: The patient inherited this mutation from his healthy mother (II:2). The patient's father (II:1) was the proband and had two VHL mutations, one of which he passed down to his son (exon 1-3 deletion). The father had hemangioblastomas and pancreatic cysts. The grandfather (I:1) had a P81S mutation but was otherwise healthy. Refer to pedigree in Figure 1-C.
CohortInfo: Patients were registrants from the European-American Pheochromocytoma-Paraganglioma and German von Hippel-Lindau Disease Registries.
CasePresentingHPOs: HP:0001737, HP:0006880, HP:0009711 (pancreatic cysts, cerebellar hemangioblastoma, retinal capillary hemangioma)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: RET/SDHB/SDHD/SDHC
PreviouslyPublished: May have been previously published in 11106358 and/or 7563486.
SupplementalData: Yes, File 1 for methods.
Variant: Exon 1-3 loss
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: N/A
CAID: N/A
gnomAD: N/A
VariantEvidence: N/A
MutationType: exon_loss_variant
CivicName: Exon 1-3 Deletion and Splice Region (c.340+5G>C)
MultipleGeneVariants: Germline, VHL, c.340+5G>C