3 Matching Annotations
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  2. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype
    1
    1. ClingenBaseline 05 Nov 2026
      P1 who has developed three tumours (Figure 1a) presents a mosaic VHL mutation (c.500G>A, p.(R167Q)) with a frequency of the mutated allele of 5.7%

      PatientID: 1

      KindredID: 1

      Case: M, 17Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: None

      CohortInfo: Eight patients whose pheochromocytomas were suggestive of VHL but were negative for a VHL abnormality both by PCR-Sanger sequencing and by quantitative multiplex PCR of short fluorescent fragments (QMPSF).

      CasePresentingHPOs: HP:0010797, HP:0002666, HP:0030405, HP:0006748 (Hemangioblastoma, Pheochromocytoma, Pancreatic endocrine tumor, adrenal pheochromocytoma)

      CaseHPOFreeText: Patient developed hemangioblastoma at age 16. At age 17 he developed right pheochromocytoma, pancreatic endocrine tumour, and a small left adrenal nodule later stated to be an adrenal pheochromocytoma.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This patient is believed to be the same as a patient published in 30731206. That paper offers more updated information on this patient.

      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: The patient had a mosaic mutation with a mutated allele frequency of 5.7%.

      MutationType: missense_variant;transition

      CivicName: R167Q (c.500 G >A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL RefSeq:NM_000551.3 NonFamilial AgeOfPresentation:hemangioblastoma:16 DiseaseEntity:hemangioblastoma DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:17 DiseaseEntity:pancreaticendocrinetumor AgeOfPresentation:pancreaticendocrinetumor:17 DiseaseEntity:adrenalpheochromocytoma AgeOfPresentation:adrenalpheochromocytoma:17 ProteinPosition:167 CivicName:R167Q(c.500G>A) cDNAposition:500 AminoAcidChange:ARGtoGLN MutationType:missense_variant;transition Mutation:Germline ClinVarID:2216 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC4135403/
  3. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    An Advanced Well-differentiated Pancreatic Neuroendocrine Carcinoma (NET-G3) Associated with Von Hippel-Lindau Disease
    1
    1. ClingenBaseline 31 Oct 2026
      45-year old Japanese woman

      PatientID: None

      KindredID: 1

      Case: F, 45Y0M, Japanese

      DiseaseAssertion: VHL

      FamilyInfo: No evidence of a family history of VHL.

      CasePresentingHPOs: HP:0001737; HP:0030405; HP:0006880; HP:0006748; HP:0009711; HP:0001732; HP:0002896 (Pancreatic cysts, Pancreatic endocrine tumor, Cerebellar hemangioblastoma, Adrenal pheochromocytoma, Retinal capillary hemangioma, Abnormality of the pancreas, Neoplasm of the liver)

      CaseHPOFreeText: The proband had a cerebellar hemangioblastoma resected at age 17, retinal hemangioblastoma surgery at age 26, and an adrenalectomy for pheochromocytoma at age 30. An abdominal CT revealed a 4cm abdominal mass and diffuse pancreatic cystic lesions, diagnosed as pancreatic neuroendocrine tumor.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText:

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q132* (c.394C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 288749, (https://www.ncbi.nlm.nih.gov/clinvar/variation/288749/)

      CAID: CA10606205 (http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA10606205)

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: Q132* (c.394C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL Mutation:Germline AminoAcidChange: GLNtoTER ProteinPosition:132 CAiD:CA10606205 MutationType:missense_variant;transition CivicName:Q132*(c.394C>T) DiseaseEntity:pancreaticcysts DiseaseEntity:pancreaticendocrinetumor DiseaseEntity:hemangioblastoma DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:abnormalityofthepancreas AgeOfPresentation:cerebellarhemangioblastoma:17 AgeOfPresentation:retinalcapillaryhemangioma:26 AgeOfPresentation:adrenalpheochromocytoma:30 cDNAposition:394 AssumedRefSeq:NM_000551.3 NonFamilial InheritancePattern:AutosomalDominant Ethnicity:Japanese ClinVarID: 288749 ClinVarID:Yes DiseaseEntity:neoplasmoftheliver inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC6096011/
  4. Oct 2026
  5. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    A Case of Von Hippel-Lindau Disease with Bilateral Pheochromocytoma and Ectopic Hypersecretion of Intact Parathyroid Hormone in an Adolescent Girl
    1
    1. ClingenBaseline 26 Oct 2026
      2. Presentation of CaseA 17-year-old girl was referred to our department for the investigation of a newly diagnosed diabetes mellitus and a severe arterial hypertension. She was the first child of consanguineous parents. Her past medical history was unremarkable. Her family history was notable for type 2 diabetes and dyslipidemia but no history of pheochromocytoma, paraganglioma, unexplained sudden death, or condition that may lead to thinking about VHL disease was reported.As symptoms, the patient complained of headaches, palpitations, diaphoresis, and hot flashes since one month. She reported also asthenia and body weight loss of five kilograms in two weeks.On examination, she had a body weight of 50 kg, a body height of 154 cm, a body mass index of 21.1 kg/m2, a blood pressure of 200/100 mmHg without orthostatic hypotension, a regular pulse of 120 bpm, and a large abdominal café-au-lait spot (Figure 1). Thyroid, abdominal, and neurological examinations were normal.Open in a separate windowFigure 1A large abdominal café-au-lait spot.Twenty-four-hour blood pressure monitoring confirmed the diagnosis of hypertension and the presence of peaks of 230/110 mmHg. Electrocardiogram showed a sinus tachycardia. Capillary glucose level was 2.68 g/l without ketosis.Fundoscopy showed grade 3 hypertensive retinopathy without any other abnormalities.The results of biological investigations are shown in Table 1.Table 1Biological parameters before and after surgery. Before surgeryAfter surgeryReference rangesFasting glucose level (mmol/l)16.394.784.12–5.55Glycated hemoglobin (%)10.125.91≤5.6Total cholesterol (mmol/l)11.835.233.1–5.18Triglycerides (mmol/l)2.431.210.57–1.71Natremia (mmol/l)135140135–145Kalemia (mmol/l)3.343.6–5Creatinine (mg/L)664–13Calcium (mg/L)111.29888–105Phosphate (mg/L)443627–45Albumin (g/l)47.22—35–52Intact PTH∗ (μg/L)1825411–62TSH (mUI/L)0.625—0.12–3.4FT4 (ng/dl)1.31—0.71–1.85Calcitonin (ng/L)2.70—<10.0024 h-urine NMN (μg/24)315057030–60024 h-urine MN (μg/24)40.21220–34524 h-urine sodium (mmol/24 h)88.5— 24 h-urine potassium (mmol/24 h)60— 24 h-urine calcium (mg/24 h)200— 24 h-proteinuria (g/24)0.3—<0.3Open in a separate windowPTH: parathormone, TSH: thyroid stimulating hormone, FT4: free-T4, NMN: normetanephrines, MN: metanephrines. ∗The intact PTH dosage was made using 3rd generation chemiluminescence immunoassay.The diagnosis of clinically suspected pheochromocytoma was confirmed by the dosage of urinary methoxylated derivatives at 5 times the upper limit of normal. In addition, the diagnosis of diabetes mellitus, dyslipidemia, and primary hyperparathyroidism were made.The abdominal computed tomography (CT) showed two adrenal masses: the first on the right measuring 35 × 55 × 70 mm with a spontaneous density of 30 HU heterogeneously enhanced in the arterial time showing areas of necrosis with an absolute washout of 40%, the second on the left measuring 24 × 27 mm with the same characteristics as the first one (Figure 2). There were neither other localizations nor lymph nodes. Metaiodobenzylguanidine (MIBG) scintigraphy exhibited a high accumulation of the tracer in both adrenal tumors with no other localization. Cervical ultrasound and 99mTc-sestamibi scintigraphy were normal. Cardiac ultrasound was normal.Open in a separate windowFigure 2Abdominal computed tomography showing the two adrenal masses (two white arrows).

      PatientID: N/A (case)

      KindredID: 1

      Case: F, 18Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Not relevant - She was the first child of consanguineous parents. Her family history was notable for type 2 diabetes and dyslipidemia but no history of pheochromocytoma, paraganglioma, unexplained sudden death, or condition relevant to VHL. However, the family screening for VHL has not been performed.

      CasePresentingHPOs: HP:0006748; HP:0000819; HP:0008200 (adrenal pheochromocytoma; Diabetes mellitus; hyperparathyroidism)

      CaseHPOFreeText: First brought to clinic for newly diagnosed diabetes mellitus and severe arterial hypertension. As symptoms, the patient complained of headaches, palpitations, diaphoresis, and hot flashes since one month. She reported also asthenia and body weight loss of five kilograms in two weeks. Pheochromocytoma was confirmed. CT showed adrenal masses: Right measuring 35×55×70mm, and left measuring 24×27mm. She underwent a bilateral adrenalectomy in two steps. Pathological examination confirmed bilateral adrenal pheochromocytomas. 12 months post, follow up is clear.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: Thyroid, abdominal, and neurological examinations were normal.

      CasePreviousTesting: RET

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R64P (c.191G>C)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2226 https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: R64P (c.191G>C)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:diabetesmellitus DiseaseEntity:hyperparathyroidism AgeOfPresentation:adrenalpheochromocytoma:17 cDNAposition:191 CivicName:R64P(c.191G>C) ProteinPosition:64 AminoAcidChange:ARGtoPRO MutationType:missense_variant;transversion ClinVarID:2226 ClinVarID:Yes NonFamilial PreviousTesting:RET inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC7428957/