PatientID: 12

KindredID: 12

Case: F, 36Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: 3/4 of her sons also carried the mutation, one of which presented with a paraganglioma.

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

CasePresentingHPOs: HP:0002668; HP:0006748; HP:0002886 (paraganglioma, adrenal pheochromocytoma, vagal paraganglioma)

CaseHPOFreeText: At 39Y (in 1993), she presented with recent onset of hypertension and was diagnosed with a right pheochromocytoma. (At age 36, a suspected left pheochromocytoma was noted by CT and confirmed at age 39 by [123I]MIBG scintigraphy). This imaging showed in addition an uptake located in the neck. MRI confirmed a left adrenal tumor and a left 2-cm vagal paraganglioma that was removed and confirmed histopathologically.

CaseNotHPOs: N/A

CaseNotHPOFreeText: No other tumor of the VHL spectrum was discovered. 

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y156C (c.467A>G)

LegacyVariant: p.Y156C

CaseProblemVariantFreeText: The publication only provides the p., the mutation was able to be deduced to p.Y156C (c.467A>G)

ClinVarID: 43600 https://www.ncbi.nlm.nih.gov/clinvar/variation/43600/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: Y156C (c.467A>G)

MultipleGeneVariants: N/A

PatientID: 186

KindredID: 72

Case: F, 39Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband, patient 72, has multiple family members with the same mutation. Her father (patient 73) had a CNS hemangioblastoma at 65, renal cell carcinioma at 54, and multiple pancreatic cysts/tumors at 67. Her sister 2 (second sister) had multiple pancreatic cysts/tumors at 36, and a CNS hemangioblastoma at 39. Her sister 3 had multiple pancreatic cysts/tumors at 32, and a retinal angioma at 34. The proband's sister 1 had a CNS hemangioblastoma at 22, but passed away before they could be diagnosed/ confirmed with the mutation.

CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001732; HP:0001737; HP:0002666 (Hemangioblastoma, Renal cell carcinoma, Abnormality of the pancreas, Pancreatic cysts, Pheochromocytoma)

CaseHPOFreeText: The patient presented with a CNS hemangioblastoma, renal cell carcinoma, and multiple pancreatic cysts/tumors at 37, and a pheochromocytoma at 39.

CaseNotHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.R167W (c.499C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: 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?dataset=gnomad_r2_1

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

PatientID: III-5

KindredID: 1

Case: M, Age Unknown, Chinese

DiseaseAssertion: Asymptomatic

FamilyInfo: In the patient’s 12 member Chinese family, 7 members were found to carry the NM_000551.3:c.114delC mutation. Five had manifestations of CNS hemangioblastoma, and three of the five were deceased. The other member found to carry the mutation were asymptomatic, although the paper states that this is likely due to their young age.

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that the patient is young, but no specific age is given.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G39Afs*28(c.114delC)

LegacyVariant: p.G39Afs*28(c.327delC)

ClinVarID: N/A

CAID: CA2573047816, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA2573047816

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: G39Afs(c.114delC)

MultipleGeneVariants: N/A

PatientID: III-3

KindredID: 1

Case: M, Age Unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: In the patient’s 12 member Chinese family, 7 members were found to carry the NM_000551.3:c.114delC mutation. Five had manifestations of CNS hemangioblastoma, and three of the five were deceased. The other two members found to carry the mutation were asymptomatic, although the paper states that this is likely due to their young age.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: The patient suffered from progressive severe neck pain and numbness of the left arm for 6 months. The patient was initially treated with opioids and antiinflammatory medications and wore rigid neck collars. Despite intense conservative therapy, the patient experienced inadequate pain relief and underwent resection of CNS hemangioblastoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G39Afs*28(c.114delC)

LegacyVariant: p.G39Afs*28(c.327delC)

ClinVarID: N/A

CAID: CA2573047816, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA2573047816

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: G39Afs(c.114delC)

MultipleGeneVariants: N/A