GroupID: 61

Case: Age Unknown, Sex Unknown, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: 1 of the 573 patients discussed in this paper were found to have this variant. This mutation (c.262T>A) was found in 1 VHL family with a single patient.

CasePresentingHPOs: HP:0005584; HP:0009711; HP:0006880 (renal cell carcinoma; retinal capillary hemangioma; cerebellar hemangioblastoma)

CaseHPOFreeText: patient had retinal angioma diagnosed at 23Y, cerebellar hemangioblastoma diagnosed at 54Y, and RCC at 54Y.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.W88R (c.262T>A)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 456577 https://www.ncbi.nlm.nih.gov/clinvar/variation/456577/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W88R (c.262T>A)

MultipleGeneVariants: N/A

PatientID: Daughter

KindredID: 1

Case: F, 35Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: Father and brother presented with the same VHL mutation. Brother presented with a meningioma, pancreatic lesions and bilateral renal cysts all at 38Y. Father presented with cerebellar hemangioblastoma 49Y, retinal hemangioblastoma 64Y, bilateral renal cell carcinoma 51Y and multiple pancreatic neuroendocrine tumors 64Y.

CohortInfo: Thirteen unrelated patients with germline VHL mutations who were diagnosed with VHL disease were evaluated.

CasePresentingHPOs: HP:0006880; HP:0005584; HP:0030405; HP:0000107 (Cerebellar hemangioblastoma, Renal cell carcinoma, Pancreatic endocrine tumor, Renal cyst)

CaseHPOFreeText: Cerebellar hemangioblastoma, renal cell carcinoma, multiple pancreatic neuroendocrine tumors and bilateral renal cysts all at 35Y. Diagnosed with VHL Type 1.

CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.M54Gfs*77 (c.160_161del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA913189210, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.160_161del

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion; minus_2_frameshift_variant

CivicName: M54Gfs*77 (c.160_161delAT)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 1

Case: F, 54Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Son (id:1) with the same variant, presenting with cerebellar hemangioblastoma at age 18, spinal hemangioblastomas at ages 19 and 31 and renal cysts but the age of onset for these is not noted. Father (id: 3) presented with cerebellar hemangioblastoma at age 65. Paternal uncle (id: 4) presented with prostate cancer at age 65. Paternal grandfather (id: 5) presented with cerebellar hemangioblastomas at age 69. Mother and daughter did not have the mutation. Her father was not tested. No family history of retinal capillary hemangiomas or pheochromocytoma.

CasePresentingHPOs: HP:0006880; HP:0005584; HP:0003002 (Cerebellar hemangioblastoma, Renal cell carcinoma, Breast carcinoma)

CaseHPOFreeText: Bilateral breast cancer at age 46 and 49. First cancer was diagnosed at the age of 46 in her right breast. The patient was treated by mastectomy with postoperative chemotherapy (CMF). Histopathological examination revealed invasive ductal breast carcinoma. A metastasis in 1 axillary lymph node was found. There was no evidence of distant metastases. Three years later, at the age of 49, she was diagnosed with cancer of her left breast. It was an invasive ductal carcinoma. There was no evidence for lymph-node or distant metastases. At present, 9 and 6 years after treatment of the breast cancers there is no evidence of breast cancer recurrence. However at age of 54, lesions typical for VHL disease including cerebellar haemangioblastoma and renal cell carcinoma were diagnosed in the patient.

CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Figure 1 (pedigree) and Table 1 (phenotype and age of onset data).

Variant: Exon 1 Deletion (c.1-?_340+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1 Deletion

MultipleGeneVariants: Germline, FANCD2, Partial Deletion