PatientID: 109

KindredID: 37

Case: M, 20Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

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

CaseHPOFreeText: The proband presented with a CNS hemangioblastoma at 19, renal cell carcinoma and multiple pancreatic cysts/tumors at 20.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in an earlier paper by Wang et al., 2014 (PMID 24581539) as well as 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.S111Tfs*48 (c.332delG)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA913189247; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.332delG

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: S111fs (c.332del)

MultipleGeneVariants: N/A

PatientID: None

KindredID: B

Case: M, 27Y0M, Hungarian

DiseaseAssertion: VHL

FamilyInfo: The parents of the patient rejected clinical and genetic screening, whereas clinical screening in a younger brother of the index patient revealed no abnormality.

CasePresentingHPOs: HP:0009711, HP:0000107, HP:0001737, HP:0001901, HP:0006880 (retinal capillary hemangioma, renal cyst, pancreatic cysts, polycythemia, cerebellar hemangioblastoma)

CaseHPOFreeText: Retina involvement presented at age 19. The patient had cerebellar hemangioma as well as renal and pancreatic cysts at the age of 27 years.

CaseNotHPOs: HP:0005584, HP:0002666 (renal cell carcinoma, pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: 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: 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

PatientID: N/A (case)

KindredID: 1

Case: F, 19Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Non-consanguineous parental relationship; second child; no mention of VHL in the family.

CasePresentingHPOs: HP:0010797; HP:0001713; HP:0002039; HP:0001824 (Hemangioblastoma; pancreatic cysts; anorexia; weight loss)

CaseHPOFreeText: Healthy from birth, this patient was referred to a psychiatric inpatient at 19Y with the weight loss and weakness, and the suspicion on anorexia nervosa. AN was not met according to the DSM-5 or ICD-10 (despite anorexic tendencies). There were also no tendencies towards an eating disorder. Patient developed progressive gait abnormality, along with bilateral dysmetria. MRI revealed a massive lesion with vascular characteristics suggestive of a HB in the fourth ventricle causing hypertensive hydrocephalus. Abdominal CT scan revealed cystic lesions throughout the parenchymatous portion of the pancreas, suspected to be related to VHLs. Together, supported the diagnosis of VHL. The patient underwent surgery of the brain, and radiotherapy which proved to work in small degrees.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: All blood tests, urinalysis and chest X‑ray were unremarkable. She also had no pheochromocytoma.

CasePreviousTesting: N/A

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