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  1. Last 7 days
  2. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Genotype-phenotype correlations in Chinese von Hippel–Lindau disease patients
    2
    1. ClingenBaseline 04 Nov 2026

      PatientID: 118

      KindredID: 42

      Case: F, Age unknown, Chinese

      DiseaseAssertion: Asymptomatic

      FamilyInfo: The proband (patient 42) had four family members confirmed with the mutation: his son (CNS hemangioblastoma at 12, retinal angioma at 11); his sister 1 (patient 116) presented with multiple pancreatic cysts/tumors at 53; his niece (daughter of sister 2) was asymptomatic at the time of assessment, and his nephew (son of brother 2) presented with a CNS hemangioblastoma at 12, and pheochromocytoma and multiple pancreatic cysts/tumors at 18. The proband also had three family members who passed away before diagnosis/ before they could be confirmed with the mutation: his sister 2 (patient 117) had multiple pancreatic cysts/tumors at 46, his brother 1 presented with a CNS hemangioblastoma at 47, renal cell carcinoma at 59, and multiple pancreatic cysts/tumors at 59; and his brother 2 presented with a retinal capillary hemangioma at 43, and CNS hemangioblastoma, renal cell carcinoma, and multiple pancreatic cysts/tumors at 44.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: The proband's niece (daughter of sister 2) was genetically confirmed with the mutation but was asymptomatic at the time of assessment.

      CaseNotHPOs: HP:0002666; HP:0005584; HP:0010797; HP:0009711; HP:0001732; HP:0001737 (Pheochromocytoma, Renal cell carcinoma, Hemangioblastoma, Retinal capillary hemangioma, Abnormality of the pancreas, Pancreatic cysts)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This cohort was also published in a paper by Wang et al., 2018 (PMID: 24581539) and Wang et al., 2014 (PMID: 29330336).

      SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

      Variant: p.W117G (c.349T>G)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 862346; https://www.ncbi.nlm.nih.gov/clinvar/variation/862346/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: W117G (c.349T>G)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:asymptomatic CivicName:W117G(c.349T>G) cDNAposition:349 ProteinPosition:117 AminoAcidChange:TRPtoGLY ClinVarID:862346 ClinVarID:Yes MutationType:missense_variant;transversion SupplementalData Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 04 Nov 2026

      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 #42. A male proband (patient 114) was diagnosed with CNS hemangioblastoma at 36Y, retinal angioma at 44Y, RCC at 44Y, and multiple pancreatic lesions at 44Y. His son (patient 115) was diagnosed with CNS hemangioblastoma at 12Y and retinal angioma at 11Y. His first sister (patient 116) was diagnosed with multiple pancreatic lesions at 53Y. His second sister (patient 117), who was not genetically confirmed for the mutation, was diagnosed with multiple pancreatic lesions at 46Y. His niece (daughter of second sister) (patient 118) was asymptomatic. His first brother (patient 119), who was not genetically confirmed for the mutation, was diagnosed with CNS hemangioblastoma at 47Y, RCC at 59Y, and multiple pancreatic lesions at 59Y. His second brother (patient 120), who was not genetically confirmed for the mutation, was diagnosed with CNS hemangioblastoma at 44Y, retinal angioma at 43Y, RCC at 44Y, and multiple pancreatic lesions at 44Y. His nephew (son of second brother) (patient 121) was diagnosed with CNS haemangioblastoma at 12Y, multiple pancreatic lesions at 18Y, pheochromocytoma at 18Y. This cohort was also published in a paper by Wang et al., 2018 (PMID: 24581539) and Wang et al., 2014 (PMID: 29330336). Wang et al., 2018 reported 8 patients from 1 family who were genetically confirmed with this germline mutation. Wang et al., 2014 reported 4 patients from 1 family who were genetically confirmed with the mutation. It is likely that all three papers published the same family.

      EvidenceStatement ClinVarID:862346 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5503545/
  3. cancerres.aacrjournals.org cancerres.aacrjournals.org
    Telomere Shortening Is Associated with Genetic Anticipation in Chinese Von Hippel–Lindau Disease Families
    2
    1. ClingenBaseline 02 Nov 2026
      c.349T>G p.Trp117Gly

      PatientID: III:7

      KindredID: 7

      Case: M, 13Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: 8 other members of this 3 generation family were observed to be affected with various presentations of VHL. This patient’s father and 3 cousins were confirmed with identical mutations. DNA samples were not available for all members in the family however.

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: had hemangioblastoma at 13Y

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.W117G (c.349T>G)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 862346 https://www.ncbi.nlm.nih.gov/clinvar/variation/862346/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: W117G (c.349T>G)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL DiseaseEntity:hemangioblastoma AgeOfPresentation:hemangioblastoma:13 ClinVarID:862346 ClinVarID:Yes ExperimentalAssay Familial FamilyPedigree Mutation:Germline AssumedRefSeq:NM_000551.3 ProteinPosition:117 CivicName:W117G(c.349T>G) cDNAposition:349 AminoAcidChange:TRPtoGLY MutationType:missense_variant;transversion inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 30 Oct 2026
      Relative telomere length assessment Genomic DNA was isolated from peripheral blood by using a blood DNA extraction kit (Tiangene). We followed the method described by Cawthon to quantify relative telomere length by measuring copy number ratio of telomere repeats (T) to the single copy gene 36B4 (S) using qRT-PCR (24). The 10-μL PCR mixture contained 2X SYBR master mix (Takara) 5 μL, genomic DNA 30 ng, 300 nmol/L telomere primer Tel1 (5′-GGTTTTTGAGGGTGAGGGTGAGGGTGAGGGTGAGGGT) and 900 nmol/L Tel2 (5′-TCCCGACTATCCCTATCCCTATCCCTATCCCTATCCCTA), or 200 nmol/L single copy gene primer 36B4u (5′-CAGCAAGTGGGAAGGTGTAATCC), and 500 nmol/L 36B4d (5′-CCCATTCTATCATCAACGGGTACAA; ref. 19). qRT-PCR was run in an ABI 7500 PCR instrument using the profile of 95°C for 30 seconds and 40 cycles of 95°C for 15 seconds, 54°C for 2 minutes, and 72°C for 15 seconds. A standard curve from a control DNA sample (male, 45 years old) by serial 1/4 dilutions from 50 ng to 0.19 ng was constructed to evaluate the amplification efficiency (E), and this sample was measured in every batch of PCRs as the inter-run calibration. Threshold cycle (Ct) values were automatically determined by the 7500 software v2.0.5. The measurements of telomere length and single copy gene 36B4 were triplicate in one batch for each sample, and the mean of the three Ct values (Cm) was used for the calculation. PCR efficiency and the calibration of copy numbers were also enrolled in the telomere length calculation (19, 25). The formula to calculate the copy number ratio of telomere repeats (T) to single copy gene 36B4 (S) is as follows, and T/S represents the value of relative telomere length. <img class="highwire-embed" alt="Embedded Image" src="https://cancerres-aacrjournals-org.uhn.idm.oclc.org/sites/default/files/highwire/canres/74/14/3802/embed/graphic-1.gif"/> The relationship between age and relative telomere length in 325 normal controls can be expressed by the linear regression equation of Y = 1.4503-0.0117*X (see Fig. 2). Normal relative telomere length at the DNA sample-obtained age can then be predicted by this equation. The difference between predicted normal relative telomere length at the DNA-obtained age and the relative telomere length actually measured was the age-adjusted relative telomere length (19), which was used for the comparison among patients with VHL in generations. Telomere length measurement by Southern blot analysis The oligonucleotide (TTAGGG)4 was tailed with DIG-dUTP as the probe by using terminal transferase. Two micrograms of genomic DNA were digested with HinfI/RsaI and separated in 0.8% agarose gel. The DNA fragments in the gel were then transferred onto a Hybond-N membrane by Southern blotting. After UV cross-link and prehybridization, the membrane was hybridized in a solution containing 2 pmol/mL probe, 50% formamide, 2× SSC, 0.1% lauroyl sarcosine, 0.02% SDS, and 1% milk powder at 42°C for 6 hours, washed at room temperature in 2× SSC, 0.1% SDS for two times, and in 0.1× SSC, 0.1% SDS, 15 minutes for two times. Hybridized probe on the membrane was recognized by alkaline phosphatase conjugated anti-DIG antibody and chemiluminescent method. The luminescent image was developed on a phosphoimager. The telomere length was calculated by a telomeric software (version 1.2; ref. 26).
      ExperimentalAssay ClinVarID:584477 ClinVarID:223172 ClinVarID:2218 ClinVarID:862346 ClinVarID:625261 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    cancerres.aacrjournals.org/content/74/14/3802
  4. Oct 2026
  5. www.frontiersin.org www.frontiersin.org
    Frequent Mutations of VHL Gene and the Clinical Phenotypes in the Largest Chinese Cohort With Von Hippel–Lindau Disease
    1
    1. ClingenBaseline 29 Oct 2026
      In this study, we analyzed the correlations between frequent mutations in the VHL gene and clinical phenotypes in the largest Chinese VHL cohort to date. In total, we screened 540 patients from 187 unrelated VHL families and identified 126 different VHL mutations. Furthermore, we identified 19 frequent mutations and four mutation hotspots and further investigated the genotype–phenotype correlations. Notably, patients or families with the VHL disease have a range of different phenotypes. A variety of factors may contribute to this diversity of phenotypes, including the type of VHL mutation, the site of the mutation, and ethnic background.

      540 patients from 187 unrelated Chinese VHL families at the Peking University First Hospital were all screened for VHL clinical features and germline mutations. Of these, clinical characteristics were observed in 258 patients from 80 unrelated Chinese families. These were reported in this study, grouped by the 21 mutations found. PCR and MLPA on peripheral blood detected the VHL mutations. Possessing the p.W117G (c.349T>G) mutation, 11 members total from 2 families were described, and phenotypic information was given for this group. With ages ranging from 12-61Y, hemangioblastomas were observed in 8/11 members, retinal capillary hemangioma in 5, renal cell carcinoma in 6, pancreatic cysts in 8, pheochromocytoma in 1 member and and in a papillary cystadenoma of the epididymis genital system tumor (epididymis or broad ligament) 1 member. See more information as this cohort has been previously published in 24581539 (as family 6 of 10 members); 29330336; and 28388566.

      EvidenceStatement ClinVarID:862346 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    frontiersin.org/articles/10.3389/fgene.2019.00867/full