PatientID: 15

KindredID: 1

Case: F, 17Y0M, Spanish

DiseaseAssertion: VHL

FamilyInfo: None

CohortInfo: 36 pediatric patients with pheochromocytomas and/or parangangliomas.

CasePresentingHPOs: HP:0002666, HP:0002668 (pheochromocytoma, paraganglioma)

CaseHPOFreeText: The patient was admitted due to hypertension and secondary diabetes mellitus. She was found to have a norepinephrine secreting bilateral pheochromocytoma at age 15 and a thoracic-abdominal paraganglioma at age 17.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX

PreviouslyPublished: Yes source unknown.

SupplementalData: N/A

Variant: p.P95R (c.284C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351750809 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.284C%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: P95R (c.284C>G)

MultipleGeneVariants: N/A

PatientID: 1 (case)

KindredID: 1

Case: F, 17Y0M, Ethnicity Unknown

DiseaseAssertion: adrenal pheochromocytoma

FamilyInfo: Her father had bilateral pheochromocytoma at the age of 13 and her grandfather had died of an unknown renal disease at the age of 50. They were both however not tested for any variants. There were no reports of hereditary cutaneous or uterine leiomyomas, renal cell cancer, neuroendocrine tumors or hemangioblastomas of the CNS/retina. Further family evaluation revealed clinical and biochemical evidence of (bilateral) pheochromocytoma in two siblings 19 and age 23. These members also had the VHL mutation, while 2 unaffected family members were negative.

CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)

CaseHPOFreeText: She had persistent episodes of high blood pressure, and was imaging led to the detection of bilateral pheochromocytoma, and underwent an adrenalectomy (which was complicated by cardiac decompensation in the context of catecholamine-induced cardiomyopathy).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: FH/RET/MAX/NF1/SDHB/SDHC/SDHD/TMEM127

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G114G (c.342T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432421783 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.342T%3EC

gnomAD: N/A

VariantEvidence: The FH variant is reported in 9/116704 alleles in the ExAC database. The VHL variant was no reported, however, an T>A transition at the same nucleotide position has been reported once in 1/121408 alleles (ExAC). Researchers suspect synonymous mutation has effects on transcript splicing (2 nucleotides into exon 2).

MutationType: synonymous_variant

CivicName: G114G (c.342T>C)

MultipleGeneVariants: Germline, FH, c.556-4A>G

PatientID: 2 MA

KindredID: 2

Case: M, 35Y0M, Ethnicity Unknown

DiseaseAssertion: Pheochromocytoma

FamilyInfo: Patient had two other affected family members: their father and sister. It does not describe how they were affected nor any diagnosis or variant.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Patient had bilateral pheochromocytoma

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB, SDHD, TMEM127

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R161*(c.481C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: R161*(c.481C>T)

MultipleGeneVariants: N/A

PatientID: 8

KindredID: 4

Case: M, 13Y0M, Spanish

DiseaseAssertion: VHL

FamilyInfo: None

CohortInfo: 36 pediatric patients with pheochromocytomas and/or parangangliomas.

CasePresentingHPOs: HP:0002666, HP:0009711, HP:0006880 (pheochromocytoma, retinal capillary hemangioma, cerebellar hemangioblastoma)

CaseHPOFreeText: The patient had a benign pheochromocytoma that was secreting norepinephrine at age 13. The patient had a retinal angioma and cerebellar hemangioma at age 12.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX

PreviouslyPublished: Yes source unknown.

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

PatientID: 5

KindredID: 7

Case: M, 17Y0M, Spanish

DiseaseAssertion: VHL

FamilyInfo: No family history, assumed de-novo, but unclear if parents were tested to confirm de-novo assertion.

CohortInfo: 36 pediatric patients with pheochromocytomas and/or parangangliomas.

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: The patient had a benign bilateral pheochromocytoma that was secreting norepinephrine at age 10. At age 17, the pheochromocytoma reoccured but this time was malignant and metastasized to the lungs.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX

PreviouslyPublished: Yes source unknown.

SupplementalData: N/A

Variant: p.R167W (c.499C>T) *The authors of this paper have seemingly called the wrong protein change for this variant.

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

CAID: N/A

gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A