Medical records of 26 patients with germline mutations of the VHL gene who had been diagnosed with VHL disease in Severance Hospital (Seoul, Republic of Korea) and Samsung Medical Center (Seoul, Republic of Korea) between 2003 and 2012 were respectively reviewed. Peripheral blood leukocytes were isolated and directly sequenced. Two patients had a germline missense mutation in the VHL gene (c.383T>C; Leu128Pro). Patient 30, 27Y female, and Patient 31, 42Y female, both presented with CNS hemangioblastoma, renal cell carcinoma and a negative family history of VHL disease. The phenotypes of patient 30 were revised from a previous report (PMID 19270817).
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3.1.3. Case 3The patient was a 38-year-old woman with a family history of VHL disease and confirmed to have a missense mutation L128P in the VHL gene, who presented with multiple bilateral renal tumors. Multiple partial nephrectomies with tumor enucleations were performed. A total of 6 tumors were identified, that ranged in size from 0.4 to 6.5 cm. Of these, 4 tumors were CCRCCs, and 2 tumors showed were diagnosed as CCPRCC (tumor sizes 0.4 and 2.5 cm) (Fig. 4). Both CCPRCCs were confined to the kidney (pT1). Immunohistochemical stains were performed, which demonstrated strong expression of CK7 and CD10 in the neoplastic cells (Fig. 5). P504S was negative. In contrast, immunohistochemical stains performed on 2 separate CCRCCs demonstrated the tumor cells to be only focally positive for CK7 and diffusely positive for CD10, vimentin, and PAX-8, whereas P504S was negative.Download : Download high-res image (334KB)Download : Download full-size imageFig. 4. Patient 3: Gross appearance of the radical nephrectomy specimen showing an extensively cystic kidney. There were multiple tumors identified. The largest tumor was a 6.5 cm CCRCC located in the interpolar areas of the kidney, which showed a characteristic gross appearance for CCRCC. There were multiple additional smaller tumors including 2 separate CCPRCCs (2.5 and 0.4 cm each).
PatientID: 3
KindredID: 3
Case: F, 41Y0M, Ethnicity Unknown
DiseaseAssertion: hemangioblastoma
FamilyInfo: Positive family history of VHL disease.
CasePresentingHPOs: HP:0006766; HP:0006770; HP:0010797 (papillary renal cell carcinoma, clear cell renal cell carcinoma, hemangioblastoma)
CaseHPOFreeText: multiple cystic, bilateral renal cysts and partial nephrectomies with tumor enucleations were performed (6 tumors total that ranged from 0.4-6.5cm); Fuhrman nuclear grade 2: identified as clear cell papillary in 2 of them, and clear cell carcinoma in 4.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: p.L128P (c.383T>C)
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: 1208816 https://www.ncbi.nlm.nih.gov/clinvar/variation/1208816/
CAID: N/A
gnomAD: N/A
VariantEvidence: diffuse staining with cytokeratin 7 (CK7) was positive + and CD10 + (rare). P504S was negative -.
MutationType: missense_variant;transition
CivicName: L128P (c.383T>C)
MultipleGeneVariants: N/A
Tags
- DiseaseEntity:clearcellrenalcellcarcinoma
- cDNAposition:383
- ClinVarID:1208816
- DiseaseEntity:papillaryrenalcellcarcinoma
- InheritancePattern:AutosomalDominant
- Mutation:Germline
- AminoAcidChange:LEUtoPRO
- DiseaseEntity:hemangioblastoma
- inferred_gene_source:ClinVar
- VHL Hypothesis Annotation
- ClinVarID:Yes
- inferred_gene_hgnc:12687
- AssumedRefSeq:NM_000551.3
- ProteinPosition:128
- CivicName:L128P(c.383T>C)
- MutationType:missense_variant;transition
- Familial
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