GroupID: None

DiseaseAssertion: VHL

GroupSize: 9

GroupNumberMales: Unknown

GroupNumberFemales: Unknown

GroupEthnicity: Unknown

GroupAgeRange: Unknown

GroupInfo: Nine individuals from 2 different families initially diagnosed with MEN-IIA were investigated. All were found to have the same (c.562C>G) missense mutation in the VHL gene.

GroupPresentingHPOs: HP:0002666; HP:0006737; HP:0002865; HP:0011781 (pheochromocytoma, extra adrenal pheochromocytoma, medullary thyroid carcinoma, thyroid C cell hyperplasia)

GroupHPOFreeText: All 9 patients had pheochromocytoma, 2 of the 9 patients (unspecified) also had thyroid C-cell tumors, 1 (unspecified) had medullary thyroid carcinoma, and 1 (unspecified) had C-cell hyperplasia. 3 of the 9 patients (unspecified) also developed extra-adrenal pheochromocytoma.

GroupNotHPOs: HP:0000843; HP:0009711; HP:0010797; HP:0000107; HP:0001737 (Hyperparathyroidism, retinal capillary hemangioma, hemangioblastoma, renal cysts, pancreatic cysts.

GroupNotHPOFreeText: None of the patients had any clinical signs of renal cancer. Two patients (unspecified) were screened for retinal, CNS, and abdominal lesions; neither had occult VHL lesions.

GroupPreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L188V (c.562C>G)

LegacyVariant: c.775C>G

CaseProblemVariantFreeText: N/A

ClinVarID: 2225, https://www.ncbi.nlm.nih.gov/clinvar/variation/2225/

CAID: CA020488

gnomAD: 0.00002121, https://gnomad.broadinstitute.org/variant/3-10191569-C-G?dataset=gnomad_r2_1

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L188V (c.562C>G)

MultipleGeneVariants: N/A

PatientID: None (Proband)

KindredID: 1

Case: F, 49Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Her daughter and son both had the same VHL gene mutation.

CasePresentingHPOs: HP:0008261, HP:0005584, HP:0006737, HP:0100561 (Pancreatic islet cell adenoma, renal cell carcinoma, Extraadrenal pheochromocytoma, spinal cord lesion )

CaseHPOFreeText: The patient was screened for disease manifestations. Abdominal magnetic resonance imaging (MRI) and computerized tomography (CT) showed pancreatic and renal masses and a para-aortic mass. At laparotomy a benign islet cell tumor, an encapsulated renal cell carcinoma of low nuclear grade and an extra-adrenal pheochromocytoma were removed. At 27 months postoperatively the patient presented with back pain and clinical signs of spinal cord compression at the T9 level. No other primary tumors could be detected despite extensive radiological investigation. Intravertebral biopsy demonstrated metastatic renal cell cancer. The spinal lesion did not respond to radiotherapy. The patient died 31 months after diagnosis and postmortem examination was declined.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P86L (c.257C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182977, https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P86L (c.257C>T)

MultipleGeneVariants: N/A