Peripheral blood from unrelated patients with pheochromocytoma was tested for mutations of proto-oncogene RET, tumor suppressor gene VHL, succinate dehydrogenase subunit D (SDHD) gene, and the succinate dehydrogenase subunit B (SDHB) gene. Of 271 patients with nonsydromic pheochromocytoma and no family history of the disease, 30 mutations were found in VHL. Multiple pheochromocytomas were statistically more frequent among patients with mutations than among patients without mutations (21 of 66 vs. 5 of 205, P<0.001). The S68W (c.203C>G) mutation was detected in the patient, referred to in the paper by c.416C>G due to a difference in transcript sequence. This missense mutation was found in the VHL gene and one patient with pheochromocytoma.

PatientID: N/A

KindredID: 2

Case: Sex, Age, Ethnicity Unknown

DiseaseAssertion: pheochromocytoma

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: Nonsyndromic pheochromocytoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB, SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.S68W (c.203C>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.S68W (c.416C>G)

ClinVarID: N/A

CAID: CA351748895 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.203C%3EG

gnomAD: N/A

VariantEvidence: PMID: 15611064 shows that S68W nearly completely abolishes the HIF1a hydroxylation dependent binding (Figure 6B) which disrupts HIF-2α degredation in 786-O (renal cell carcinoma) cells (Figure 6 D).

MutationType: missense_variant; transversion

CivicName: S68W (c.203C>G)

MultipleGeneVariants: N/A

Of 16 patients presenting with clinical VHL features that underwent genetic testing, patient 1 presented with the c.203C>G mutation of the VHL gene (stated in the paper as c.416C>G which used the Latif sequence as reference). Peripheral blood lymphocytes were collected and products of the polymerase chain reaction performed on this sample were analyzed with single-stranded conformational polymorphism analysis (SSCP), PCR sequencing and Southern analysis. This missense mutation was confirmed using restriction fragment length polymorphism or allele-specific oligonucleotide analysis. This patient has a family history of multiple tumor types indicative of VHL disease but the family did not undergo genetic testing. This patient presented with a pheochromocytoma.