PatientID: 26

KindredID: 19

Case: M, 47Y0M, Brazilian (Latino/Admixed American)

DiseaseAssertion: VHL

FamilyInfo: They had a 14Y family member (ID:27), however their relation is unclear.

CasePresentingHPOs: HP:0002666; HP:0030405; HP:0009711; HP:0000107 (pheochromocytoma, pancreatic endocrine tumor, retinal capillary hemangioma, renal cyst)

CaseHPOFreeText: The patient at 13Y was confirmed with VHL. He developed bilateral pheo at 13Y, which had recurrence at 48M later. He later at 47Y he developed a PNET. He also had renal cysts and retinal HB

CaseNotHPOs: HP:0002668; HP:0001737; HP:0010797; HP:0005584 (paraganglioma, pancreatic cyst, hemangioblastoma, renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T124I (c.371C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 36902 https://www.ncbi.nlm.nih.gov/clinvar/variation/36902/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: T124I (c.371C>T)

MultipleGeneVariants: N/A

PatientID: 7

KindredID: 7

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: No family information provided.

CasePresentingHPOs: HP:0002666; HP:0002668 (Pheochromocytoma; paraganglioma)

CaseHPOFreeText: Patient had pheochromocytoma and/or paraganglioma (table 2).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T124I (c.371C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 36902, https://www.ncbi.nlm.nih.gov/clinvar/variation/36902/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant, transition

CivicName: T124I (c.371C>T)

MultipleGeneVariants: N/A

Genomic DNA was extracted from whole blood samples for genetic testing of SDHB, SDHC, SDHD, and VHL. 27 patients with urinary bladder paragangliomas, revealed 17 germline mutations, three of which were in the VHL gene. PCR–based bidirectional sequencing was performed along with MLPA on large deletions. This missense mutation (p.T124I) was found in a 12-year-old male (patient no. 22), with his urinary bladder paraganglioma diagnosis at 6Y of age. Family history of pheo or paragangliomas was said to be positive.

“None of the novel mutations were represented in 120 alleles from normal subjects in the Brazilian population suggesting that these base changes are not common polymorphisms.”