PatientID: 122

KindredID: 43

Case: F, Age 26Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband (patient 122) had a father who was genetically confirmed with the mutation. The patient's father presented with a CNS hemangioblastoma at 27, renal cell carcinoma at 48, and multiple pancreatic cysts/ tumors at 60.

CasePresentingHPOs: HP:0010797; HP:0001737; HP:0001732 (Hemangioblastoma, Pancreatic cysts, Abnormality of the pancreas)

CaseHPOFreeText: The proband presented with a CNS hemangioblastoma at 19, and multiple pancreatic cysts/tumors at 26.

CaseNotHPOs: HP:0005584; HP:0002666; HP:0009711 (Renal cell carcinoma, Pheochromocytoma, 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.W117R (c.349T>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753664; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.349T%3EA

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117R (c.349T>A)

MultipleGeneVariants: N/A

A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were included for analysis. This familial mutation was confirmed in family #43 with 2 affected members that were both genetically confirmed for the mutation. A female proband was diagnosed with CNS hemangioblastoma at 19Y and multiple pancreatic lesions at 26Y. Her father was diagnosed with CNS hemangioblastoma at 27Y, renal cell carcinoma at 48Y, and multiple pancreatic lesions at 60Y. This cohort was also published in a paper by Wang et al., 2018 (PMID: 29330336). It is likely that both papers published the same family.

PatientID: I:2

KindredID: 1

Case: F, Age Unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: Case III:1 (this patients daughter) was a 32 year old female who complained of blurred vision for the past 2 years in her left eye. Fundus examinations showed several retinal hemangioblastomas in the temporal area of the left eye. They had previously undergone the operation for cerebellar hemangioblastoma 3 years prior. Case III:2 (this patient’s grandson) was a 6 year old male who had fundus examination that revealed a very small hemangioblastoma in the distant peripheral retina of his right eye, while his left eye was normal. Case III:2 (this patient’s granddaughter) was a 12 year old female whose fundus examinations revealed a small hemangioblastoma in the infratemporal region of the peripheral retina in her right eye. A sizeable hemangioblastoma with 2.5 papilla diameters and prominant feeder vessels were detected in the inferior peripheral retina of her left eye

CasePresentingHPOs: HP:0005584 (Renal cell carcinoma)

CaseHPOFreeText: had blindness in one eye and died of renal carcinoma

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117R (c.349T>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753664 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.349T%3EA

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_transversion

CivicName: W117R (c.349T>A)

MultipleGeneVariants: N/A

PatientID: None (father)

KindredID: 1

Case: M, 78Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: 37Y old daughter had multiple cysts (RCC) in both kidneys and the same (c.349T>A) mutation

CasePresentingHPOs: HP:0000107; HP:0005584; HP:0006770 (renal cysts; renal cell carcinoma, clear cell renal cell carcinoma)

CaseHPOFreeText: VHL patient underwent left nephrectomy and right partial nephrectomy (subtotal nephrectomy). Histopathological examination revealed clear cell type renal cell carcinoma (RCC)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117R (c.349T>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753664 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.349T%3EA

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117R (c.349T>A)

MultipleGeneVariants: N/A