5 Matching Annotations
  1. Last 7 days
  2. jmg-bmj-com.uhn.idm.oclc.org jmg-bmj-com.uhn.idm.oclc.org
    Evidence for genetic anticipation in vonHippel-Lindau syndrome
    1
    1. ClingenBaseline 04 Nov 2026

      PatientID: 47 (Uncle)

      KindredID: 18

      Case: M, 39Y0M, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 11 members of this family tested positive for the c.712C>T/c.499C>T germline variant of the VHL gene. 14 members of this family were assumed to carry this variant due to family history/personal medical history. Members of this family range from asymptomatic to multi-organ involvement (pheochromocytoma, pancreatic and renal cysts/tumors and hemangioblastomas). The family was previously reported in PMID 3942913.

      CasePresentingHPOs: HP:0010797; HP:0009711 (Hemangioblastoma, Retinal capillary hemangioma)

      CaseHPOFreeText: This patient presented with CNS hemangioblastoma (30 and 42Y) and retinal angioma (26Y). Patient died at 39Y.

      CaseNotHPOs: HP:0005584; HP:0000077; HP:0001732; HP:0002666 (Renal cell carcinoma, Abnormality of the kidney, Abnormality of the pancreas, Pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 3942913 (some members of this family are previously reported (phenotypes only) but unable to match patients across papers with confidence)

      SupplementalData: Supplementary Table 1.

      Variant: N/A

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Authors state that the c.712C>T germline familial variant of the VHL gene in this patient is “inferred from the family”. No genetic testing was done on this patient to confirm this. Being that this familial variant is out of bound with respect to the NM_000551.3 reference sequence, it was concluded that this variant is noted in the Latif et al. (1993) reference and was translated to c.499C>T (NM_000551.3).

      MutationType: N/A

      CivicName: N/A

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:hemangioblastoma:42 AgeOfPresentation:hemangioblastoma:30 AgeOfPresentation:retinalcapillaryhemangioma:26 cDNAposition:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:N/A Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    jmg-bmj-com.uhn.idm.oclc.org/content/55/6/395
  3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Genotype phenotype correlation in Asian Indian von Hippel–Lindau (VHL) syndrome patients with pheochromocytoma/paraganglioma
    1
    1. ClingenBaseline 01 Nov 2026

      PatientID: 20

      KindredID: 10

      Case: M, 42Y0M, Indian

      DiseaseAssertion: VHL

      FamilyInfo: No relevant family history.

      CohortInfo: This retrospective study was conducted at Department of Endocrinology of a tertiary care health centre in Western India. Patients presented to our institute between 2008 and 2016 were included in the study. During the study period a total of 33 patients were suspected to have VHL syndrome based on clinical features among whom 31 patients were found to have mutation in VHL gene. All patients are of Asian Indian descent.

      CasePresentingHPOs: HP:0002666; HP:0010797 (Pheochromocytoma, Hemangioblastoma)

      CaseHPOFreeText: Unilateral pheochromocytoma.

      CaseNotHPOs: HP:0009711; HP:0001737; HP:0005584; HP:0030405; HP:0002668 (Retinal capillary hemangioma, Pancreatic cysts, Renal cell carcinoma, Pancreatic endocrine tumor, Paraganglioma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.L163F (c.487C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 480772, https://www.ncbi.nlm.nih.gov/clinvar/variation/480772/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: L163F (c.487C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:DeNovoAssertion Ethnicity:Indian DiseaseEntity:VHL DiseaseEntity:pheochromocytoma DiseaseEntity:hemangioblastoma AgeOfPresentation:pheochromocytoma:42 AgeOfPresentation:hemangioblastoma:42 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:487 ProteinPosition:163 AminoAcidChange:LEUtoPHE ClinVarID:480772 ClinVarID:Yes MutationType:missense_variant;transition CivicName:L163F(c.487C>T) NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/29124493/
  4. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Germline mutations in the VHL gene associated with 3 different renal lesions in a Chinese von Hippel-Lindau disease family
    1
    1. ClingenBaseline 01 Nov 2026
      A 42-year-old man was admitted to our Urology unit with a one-year history of repeating left lumbago. Ten years ago, this patient received gamma knife treatment for cerebral hemangioblastomas. There was no history of hypertension disease (blood pressure at admission: 134/79mmHg). Eyesight and fundus examinations were normal.Prior to the operation, levels of blood creatinine and urea nitrogen were normal (82 μmol/L and 6.05 mmol/L, respectively). However, the routine urine test showed an elevated level of RBCs with 9,298 cells per liter. Common tumor markers such as AFP, CEA, and PSA were normal. Magnetic resonance (MR) of the abdomen showed multiple solid lesions in the bilateral kidneys (53 mm was the largest diameter) with enhanced density after contrast, multilocular renal cysts, a right adrenal nodule, multiple cysts and a solid lesion in the pancreas (42.7 mm was the largest diameter), and multiple cysts in the liver with 2 highly vascular lesions located in the S7/8 and S2 sections (Fig. 1A and 1B). Special tests for adrenal lesions included plasma cortisol, renin angiotensin aldosterone, and urinary VMA, which were normal. The patient underwent 3 consecutive surgeries. The first surgery was partial nephrectomy that removed most of the tumors in the right kidney. Three weeks later, the second surgery removed most of the tumors on the surface of the left kidney, and radiofrequency ablation guided by ultrasound aided in treating the inner tumors. Two weeks after the second surgery, the patient received an emergency nephrectomy on the left side kidney due to a severe hemorrhage. Open in a separate windowFigure 1.Imaging findings of 2 patients. (A) and (B) Abdomen magnetic resonance (MR) of the brother (II:1) showed a solid lesion (1) and multiple cysts (2) in the pancreas; liver vascular lesion located in the S7/8 section (3); solid lesions (4) and multilocular renal cysts (5) in the kidney; and a right adrenal nodule (6). (C) Scrotum magnetic resonance (MR) of the brother (II:1) showed a malignant tumor in the right side epididymis (arrow). (D) Abdomen computed tomography (CT) of the sister (II:6) showed multiple cysts in the pancreas (7) and a right adrenal nodule (8).Pathologic reviews and an immunohistochemical test (IHC) were performed to confirm the diagnosis. Tumor sections from the right side kidney stained with hematoxylin and eosin (H&E) showed sheet-like, solid clear cells in the tumor lesions and cysts lined by clear cells with uniform nuclei in some areas (Fig. 2A and 2B). The pathological manifestations confirmed ccRCC concurrent with simple renal cysts. The left side kidney showed multilocular cysts lined by clear cells with plenty of plasm and high nuclear to cytoplasmic ratios by microscopy. Clusters of clear cells were present in the septal walls (Fig. 2C), and mcRCC was confirmed pathologically. The IHC staining of the bilateral kidney tumor was positive for CD10, CK and Vim (data not shown). Open in a separate windowFigure 2.Pathological images of the brother. (A) Clear cell renal cell carcinoma (ccRCC) from the right kidney. The tumor consists of sheet-like, solid clear cells (H&E 40×).The image in the yellow-boxed area displays part (B). Multilocular renal cysts with clear cell renal carcinoma from the right kidney. The yellow-boxed area displays a renal cyst that is lined by a single-layer of clear cells with uniform nuclei (H&E 100×). Additionally, the green-boxed area displays part of the ccRCC with sheet-like, solid clear cells. (C) Cystic renal cell carcinoma from the left kidney. Cysts are lined by clear cells with uniform nuclei. Clusters of clear cells are present in the septal walls (H&E 40×). The image in the yellow-boxed area displays the aggregates of similar-appearing clear cells scattered without permeating the septa and forming solid nodules (H&E 100×).During this patient's hospitalization, a mass was palpable in his right side scrotum, which had no tenderness, redness or itching. The scrotum MR suspected a malignant tumor on the right side epididymis (Fig. 1C). However, the patient refused to accept a biopsy of this mass.

      PatientID: II:1 (proband)

      KindredID: 1

      Case: M, 42Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: The proband presented with VHL Type 2B. Sister presented with features of VHL Type 2A including cerebral hemangioblastomas, a right adrenal nodule, multiple cysts in the pancreas, multiple cysts in the liver, two brain lesions. The younger brother and their deceased father had hemangioblastomas in the central nervous system and ocular diseases, respectively. Despite having no information of detailed clinical data, it is reasonable to assume that they had VHL diseases. The father was also blind, but the reasons are unknown. The mother had no history of disease. Pedigree: see Figure 3.

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0006770; HP:0030421 (Hemangioblastoma, Renal cell carcinoma, Clear cell renal cell carcinoma, Epididymal neoplasm)

      CaseHPOFreeText: Ten years prior (at the age of 32), the patient received gamma knife treatment for cerebral hemangioblastomas. Magnetic resonance (MR) of the abdomen showed multiple solid lesions in the bilateral kidneys, multilocular renal cysts, a right adrenal nodule, multiple cysts and a solid lesion in the pancreas, and multiple cysts in the liver. The pathological manifestations confirmed ccRCC concurrent with simple renal cysts. The left side kidney showed multilocular cysts lined by clear cells. Pathology confirmed the presence of clusters of clear cells. mcRCC was confirmed pathologically. Scrotum MR suspected a malignant tumor on the right side epididymis.

      CaseNotHPOs: HP:0000822; HP:0100631 (Hypertension, Neoplasm of the adrenal gland)

      CaseNotHPOFreeText: No history of hypertension disease. Common tumor markers such as AFP, CEA, and PSA were normal. Special tests for adrenal lesions included plasma cortisol, renin angiotensin aldosterone, and urinary VMA, which were normal.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: c.340+5G>C

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 36901, https://www.ncbi.nlm.nih.gov/clinvar/variation/36901/

      CAID: CA020288, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA020288

      gnomAD: 0.01119, https://gnomad.broadinstitute.org/variant/3-10183876-G-C

      VariantEvidence: Direct sequencing of DNA strands revealed 2 recurrent mutations of c.256C > T (p.P86S) and c.340 + 5G > C. Haplotype construction displayed that the c.256C > T (p.P86S) mutation in cis with c.340 + 5G > C were located on the disease haplotype. Bioinformatics analysis revealed that this mutation might severely destabilize the hydrophobic core of pVHL and cause VHL manifestations. This variant’s large allele frequency means this is likely non disease causing (not deleterious).

      MutationType: splice_site_variant

      CivicName: P86S (c.256C>T) and Splice Region (c.340+5G>C)

      MultipleGeneVariants: Germline, VHL, c.256C>T (p.Pro86Ser)

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:epididymalneoplasm DiseaseEntity:hemangioblastoma AgeOfPresentation:hemangioblastoma:32 AgeOfPresentation:renalcellcarcinoma:42 AgeOfPresentation:epididymalneoplasm:42 AgeOfPresentation:clearcellrenalcellcarcinoma:42 Mutation:Germline RefSeq:NM_000551 AssumedRefSeq:NM_000551.3 ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:36901 ClinVarID:Yes CAID:CA020288 MultipleVHLVariants MutationType:splice_site_variant CivicName:P86S(c.256C>T)andSpliceRegion(c.340+5G>C) FamilyPedigree Familial cDNAposition:N/A CompoundHeterozygous inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC4990403/
  5. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Endolymphatic sac tumor with von Hippel-Lindau disease: report of a case with atypical pathology of endolymphatic sac tumor
    1
    1. ClingenBaseline 30 Oct 2026
      A 42-year-old female was admitted with complaints of a 15-day history of intermittent headaches and dizziness, without nausea and vomiting. Computed tomography (CT) revealed a giant mass lesion with mixed density in the right CPA region along with the destroyed petrous bone (Figure 1A), and a low density space-occupying lesion in the left cerebellar hemisphere. No abnormal physical and laboratory examination including abdominal CT, were found except for a past history of appendicitis excision and cesarean section and the impairment of right hearing resulting from otitis media in childhood. Cranial magnetic resonance imaging (MRI) described two tumors that were 4 × 3 × 3 cm in size in the right CPA region with mixed-signal intensity on T1, T2-weighted images and heterogeneous contrast enhancement; and 4.1 × 2.5 × 3.0 cm in size in the left cerebellar hemisphere with being obviously cystic change (Figure 1B-E). The boundary of two lesions were relatively clear from surrounding parenchyma.Open in a separate windowFigure 1Radiologic characterization of endolymphatic sac tumor and hemangioblastoma. A: CT imaging demonstrated a destroyed petrous bone involving the right mastoid and the middle ear. B-E: MR scan showed two giant masses co-existing in the posterior cranial fossa. The right one in the CPA was irregular, heterogeneous on T1/T2-weighted images as well as heterogeneous contrast enhancement, the left lesion was shown with solid and cyst change in cerebellar hemisphere. F: MRI scan after the second operation showed totally resection of both lesions.Operation and pathological findingsBoth tumors were completely removed via right and left retrosigmoid sinus craniotomy respectively within 25 days. During the first operation, lesion with demarcating from normal cerebellar tissue and invading part of petrous bone were found. The origin of the tumor from petrous bone could be apparently observed. In the second operation, the brown cyst fluid associated with old hemorrhage and soft solid nodule were seen. Under a microscope observation after the first surgery, intense vascularization of the tumor and the obviously primarily cystic architecture were observed. The cystic architecture filled with colloid-like material. Most of them were lined by a single layer of flattened epithelial cells, few covered by a single layer of cuboidal to columnar cells (Figure 2A-D). Immunohistochemical staining demonstrated vascular cells positive reactivity for CD31 (Figure 3A) and CD34 (Figure 3C), which were mistaken for the tumor cells at the initial diagnosis. Subsequently, further immunohistochemical staining showed positive reactivity for PAS (Figure 3B), epithelial membrane antigen (EMA) (Figure 3D), NSE and cytokeratin (CK) but negative for D2-40 and S-100. As to another specimen, histological examination shown round-to-oval nuclei and abundant clear cytoplasms in most of cells (Figure 4). Immunohistochemical staining confirmed hemangioblastoma.

      PatientID: 1

      KindredID: 1

      Case: F, 42Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797; HP:0030393; HP:0002315; HP:0002321 (Hemangioblastoma, Endolymphatic sac tumor, Headache, Vertigo)

      CaseHPOFreeText: Admitted with complaints of a 15-day history of intermittent headaches and dizziness, without nausea and vomiting. Computed tomography (CT) revealed a giant mass lesion with mixed density in the right CPA region along with the destroyed petrous bone, and a low density space-occupying lesion in the left cerebellar hemisphere. Cranial MRI described two tumors in the right CPA region and in the left cerebellar hemisphere. A classic radiological feature of hemangioblastoma was observed in the left cerebellar hemisphere which was supported by post-operative biopsy.

      CaseNotHPOs: HP:0002012 (Abnormality of the abdominal organs)

      CaseNotHPOFreeText: No abnormal physical and laboratory examination, including abdominal CT, were found.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Y98Afs*37 (c.282_291dup)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA2573050500, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA2573050500

      gnomAD: N/A

      VariantEvidence: 291st site of Exon 1 was insertion of 10 nucleotides (GCCGCAGCCC).

      MutationType: plus_1_frameshift_variant; duplication

      CivicName: p.Y98Afs (c.282_291dup)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:endolymphaticsactumor DiseaseEntity:vertigo DiseaseEntity:headache AgeOfPresentation:hemangioblastoma:42 AgeOfPresentation:endolymphaticsactumor:42 AgeOfPresentation:vertigo:42 AgeOfPresentation:headache:42 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:292 ProteinPosition:98 AminoAcidChange:TYRtoALA ClinVarID:N/A MutationType:plus_1_frameshift_variant CivicName:p.Y98Afs(c.282_291dup) NoFamilyInfo CAID:CA2573050500 MutationType:duplication inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC4069932/
  6. Oct 2026
  7. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Genotype-phenotype correlations in Chinese von Hippel–Lindau disease patients
    1
    1. ClingenBaseline 21 Oct 2026

      PatientID: 271

      KindredID: 105

      Case: F, 42Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: N/A

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

      CaseHPOFreeText: The proband presented at age 48 with renal cell carcinoma, multiple pancreatic cysts/tumors, and pheochromocytoma.

      CaseNotHPOs: HP:0009711; HP:0005584; HP:0002666 (Retinal capillary hemangioma, Renal cell carcinoma, Pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This cohort 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: Exon 2 Deletion (c.341-?_463+?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 2 Deletion

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:abnormalityofthepancreas DiseaseEntity:pancreaticcysts AgeOfPresentation:hemangioblastoma:42 AgeOfPresentation:pancreaticcysts:36 AgeOfPresentation:abnormalityofthepancreas:36 MutationType:exon_loss_variant UnregisteredVariant CivicName:Exon2Deletion SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5503545/