Hypothesis

NRFVHLVHL p.Tyr98HisNRNRCarotid bodyPositiveRetinal hbl, Pheo, PcCyNo

PatientID: 23

KindredID: 23

Case: F, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Positive family history.

CasePresentingHPOs: HP:0002666, HP:0002864, HP:0009711, HP:0001737 (pheochromocytoma, paraganglioma of head and neck, retinal capillary hemangioma, pancreatic cysts)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 9880225

SupplementalData: N/A

Variant: p.Y98H (c.292T>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2223 https://www.ncbi.nlm.nih.gov/clinvar/variation/2223/

CAID: N/A

gnomAD: 0.00001343 https://gnomad.broadinstitute.org/variant/3-10183823-T-C

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: Y98H (c.292T>C)

MultipleGeneVariants: N/A

InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:NM_000551.3 DiseaseEntity:VHL Familial DiseaseEntity:pheochromocytoma DiseaseEntity:Paragangliomaofheadandneck DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticcysts PreviousTesting:RET ProteinPosition:98 CivicName:Y98H(c.292T>C) cDNAposition:292 AminoAcidChange:TYRtoHIS MutationType:missense_variant;transition ClinVarID:Yes ClinVarID:2223 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation

In 1994, a 34-yr-old woman without personal and familial history for VHL was referred to the hospital because of persistent pharyngeal discomfort. MRI demonstrated a 4-cm tumor in the parapharyngeal space suggestive of a schwannoma or a carotid paraganglioma. The tumor was removed, and histology revealed a paraganglioma. Postoperatively, she had Horner’s syndrome and a transitory hypoglossal paresis. At age 46, bilateral adrenal pheochromocytoma and a paraaortic paraganglioma were removed. Later, her niece was diagnosed with a pheochromocytoma, and her brother suffered from pheochromocytoma, renal cell carcinoma, and retinal hemangioblastomas. The proband’s mother was then found to have pheochromocytoma. Molecular analysis identified the VHL mutation p.Tyr98His.

PatientID: 10

KindredID: 10

Case: F, 46Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: The patient's niece was diagnosed with a pheochromocytoma, her brother suffered from pheochromocytoma, renal cell carcinoma, and retinal hemangioblastomas, and her mother was found to have pheochromocytoma.

CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

CasePresentingHPOs: HP:0002864, HP:0002277, HP:0006748 (Paraganglioma of head and neck, Horner syndrome, adrenal pheochromocytoma)

CaseHPOFreeText: At age 34 the patient was found to have a 4-cm tumor in the parapharyngeal space. It was histologically confirmed to be a paraganglioma. Postoperatively, she had Horner’s syndrome and a transitory hypoglossal paresis. At age 46, bilateral adrenal pheochromocytoma and a paraaortic paraganglioma were removed.