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: 1

KindredID: 1

Case: F, 13Y0M, Indian

DiseaseAssertion: VHL

FamilyInfo: 3 other members of this family were included in this study and all had the same VHL variant. Patient 3 (Gen 2) presented with bilateral pheochromocytoma and died due to a ruptured aortic aneurysm of Takayasu arteritis. Patient 4 (Gen 2) presented with bilateral pheochromocytoma. Patient 2 (Gen 1) presented with unilateral pheochromocytoma, PNET and died due to metastatic PNET.

CohortInfo: This retrospective study was conducted at Department of Endocrinology of a tertiary care health centre in Western India. Patients presented to our institute between 2008 and 2016 were included in the study. During the study period a total of 33 patients were suspected to have VHL syndrome based on clinical features among whom 31 patients were found to have mutation in VHL gene. All patients are of Asian Indian descent.

CasePresentingHPOs: HP:0002666; HP:0002668; HP:0030405 (Pheochromocytoma, Paraganglioma, Pancreatic endocrine tumor)

CaseHPOFreeText: Bilateral pheochromocytoma and sympathetic paraganglioma. Metastasis found at age 13. Age of onset for pheochromocytoma and paragangliomas is stated as 6, 9 and 13Y but it is not clear which age pertains to which phenotype.

CaseNotHPOs: HP:0005584; HP:0001737; HP:0009711; HP:0010797 (Renal cell carcinoma, Pancreatic cysts, Retinal capillary hemangioma, Hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R161Q (c.482G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182983, https://www.ncbi.nlm.nih.gov/clinvar/variation/182983/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R161Q (c.482G>A)

MultipleGeneVariants: N/A

PatientID: 10

KindredID: 4

Case: M, 13Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Four other family members were found to have the same mutation (Patients 6,7,8,9).

CasePresentingHPOs: HP:0002668, HP:0002666, HP:0030405 (Paraganglioma, pheochromocytoma, pancreatic endocrine tumor)

CaseHPOFreeText: The patient was diagnosed with a pancreatic endocrine tumor at age 13 it was found to be 0.7cm in size. He was diagnosed with pheochromocytoma and paraganglioma at age 12. He was found to have a right side pheochromocytoma measuring 5.5 cm and a left side pheochromocytoma measuring 1.5 cm. He was also found to have a paraganglioma measuring 2.2 cm.

CaseNotHPOs: HP:0009711, HP:0001737, HP:0000107, HP:0005584, HP:0010797 (retinal capillary hemangioma, pancreatic cysts, renal cyst, renal cell carcinoma, hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167Q (c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

CAID: N/A

gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

VariantEvidence:N/A

MutationType: missense_variant;transition

CivicName: R167Q (c.500 G >A)

MultipleGeneVariants: N/A