Approximately 1 year after IV:6 was diagnosed with VHL, her father (III:4) developed hematuria. Evaluation and subsequent treatment confirmed disease consistent with VHL, including clear-cell renal-cell carcinoma, renal cysts, pancreatic cysts, and multiple hemangioblastomas of the cerebellum and lower brainstem (fig. 2D). Southern blot analysis and DNA sequencing of the VHL gene in the father's PBLs were negative (fig. 4A) by the initial genetic testing
PatientID: III-4
KindredID: 2
Case: F, 48Y0M, Ethnicity Unknown
DiseaseAssertion: VHL
FamilyInfo: The patient’s 23Y daughter was diagnosed with VHL disease and spinal cord hemangioblastomas at 15Y. At 20Y, she had multiple cystic lesions in the right kidney, a solid lesion of the left kidney, multiple pancreatic cysts, and a small peripheral retinal angioma. She was also found to carry the same NM_000551.3:c.227_229del mutation the patient carried. The patient’s daughter’s mother was unaffected. Of the patient’s three other daughters and two brothers, one underwent clinical examination and two underwent genetic testing of unclear nature, and were found to be unaffected. The remaining two children of the patient were not evaluated.
CasePresentingHPOs: HP:0006880; HP:0001737; HP:0000107; HP:0006770 (Cerebellar hemangioblastoma, pancreatic cyst, renal cyst, clear cell renal cell carcinoma)
CaseHPOFreeText: The age 48Y patient originally presented with hematuria at age 39Y, and further investigation found clear-cell renal-cell carcinoma, renal cysts, pancreatic cysts, and multiple hemangioblastomas of the cerebellum and lower brainstem. Initial southern blot analysis and DNA sequencing of the VHL gene in the patient’s peripheral blood lymphocytes were negative; however, application of additional methods directed specifically at the region of the mutation found in the patient’s daughter (IV-6) discovered that approximately one-seventh of the patient’s peripheral blood lymphocytes carried the same VHL mutation the patient’s daughter carried, suggesting mosaic VHL disease.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: p.F76del(c.226_228delTTC)
LegacyVariant: p.F76del(c.439_441delTTC)
ClinVarID: N/A
CAID: CA357012
gnomAD: N/A
VariantEvidence: Southern blot analysis and DNA sequencing of the VHL gene in the father's PBLs were negative (fig. 4A) by the initial genetic testing, on the basis of standard methods that identified VHL mutations in 99 of 99 (Stolle et al. 1998) and in a subsequent total of 131 of 131 (Glenn et al. 1999) affected individuals. However, genetic testing of the daughter's (IV:6) PBLs by direct sequencing revealed a 3-bp deletion (TTC) at nucleotides 439–441 (fig. 4B). After identification of the mutation in IV:6, the father's DNA was again analyzed, by application of additional methods directed specifically at the region of the 3-bp deletion
MutationType: inframe_deletion
CivicName: F76del(c.226_228delTTC)
MultipleGeneVariants: N/A