2 Matching Annotations
  1. Oct 2026
  2. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Comorbid VHL and SCA2 mutations in a large kindred: confounding diagnosis of neurological dysfunction caused by CNS VHL vascular tumours versus SCA2 atrophic neurodegeneration
    1
    1. ClingenBaseline 29 Oct 2026

      PatientID: I-1

      KindredID: 1

      Case: F, 54Y0M (deceased), Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Large multigenerational family with a history of both VHL and spinocerebellar ataxia type 2 (SCA2). Screening for clinical and genetic diagnostics were gathered as well as thorough information on non-living members. I-1 had 16 children, with many grand/great/great grand children. See family pedigree (Fig. 1).

      CasePresentingHPOs: HP:0002090 (Pneumonia)

      CaseHPOFreeText: Patient was thought to have had olivopontocerebellar atrophy (OPCA) for much of her adult life. Her OPCA is now explained by the detection in her kindred of spinocerebellar ataxia type 2 (SCA2). Her VHL was diagnosed at the age of 48 years. She died of pneumonia aged 54 years.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.E160Sfs*10 (c.477delA)

      LegacyVariant: c.688delA

      CaseProblemVariantFreeText: c.477del, p.Glu160Serfs10 should be used. Details: 477del same as 475delA bc that codon is AAA so doesn't matter which A gets deleted: there is an A at 475 476 477 so for HGVS we say that 477 (the latter) is deleted since that follows HGVS nomenclature. Thus use c.477del: p.Glu160Serfs10

      ClinVarID: 182959 https://www.ncbi.nlm.nih.gov/clinvar/variation/182959/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: minus_1_frameshift_variant

      CivicName: E160fs (c.477del)

      MultipleGeneVariants: SCA2 (an abnormal increase in CAG repeats in one allele of her ataxin-2 gene. This abnormal trinucleotide expansion is consistent with the diagnosis of spinocerebellar ataxia type 2)

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:Pneumonia AgeOfPresentation:VHL:48 AgeOfPresentation:pneumonia:54 Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:477 ProteinPosition:160 ClinVarID:182959 ClinVarID:Yes MutationType:minus_1_frameshift_variant CivicName:E160fs(c.477del) AminoAcidChange:GLUtoSER MultipleGeneVariants Familial FamilyPedigree ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1735181/
  3. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Acute myeloid leukemia in a 38-year-old hemodialyzed patient with von Hippel-Lindau disease
    1
    1. ClingenBaseline 22 Oct 2026
      We observed 38-year-old hemodialyzed male patient diagnosed with von Hippel-Lindau disease in 2008 who was admitted to the Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia in Katowice with significant anemia, increased number of leukocytes, pneumonia and with suspected endocarditis.In June 2007 the patient underwent right nephrectomy for renal cell carcinoma and then in October 2007 he had surgery to remove a tumor from his brainstem (medulla oblongata) at the level of the posterior portion of the foramen magnum. Histological examination found hemangioblastoma which might have occurred as a feature of VHL disease.In 2008 the Department of Genetics and Pathology, Pomeranian Medical University in Szczecin detected a constitutional mutation 407 C/T (F136S) within the VHL gene. Study of the patient’s family history showed that his father, uncle and grandmother were diagnosed with renal cell cancer. The patient underwent annual screening program in order to identify cancer manifestations early.In October 2010, he was diagnosed with a solitary kidney tumor and qualified for surgical treatment. Histological examinations showed the tumor to be renal cell carcinoma. Postoperative course was complicated by massive hematuria leading to urgent nephrectomy resulting in chronic hemodialysis.In March 2011, he was diagnosed with dilated cardiomyopathy and complex valves defect. In May 2011, severe central sleep apnea was determined.In July 2011, patient was admitted to the hospital again. Blood tests showed anemia (HGB = 5, 6 g/dl), leukocytosis (WBC = 13×109/l) and moderate thrombocytopenia ( PLT = 72×109/l). There was no peripheral blood smear done.Gastroscopy revealed erosive gastritis. He required blood transfusion during the hospitalization. Following tests reported increasing number of white blood cells (up to 55×109/l) and reducing number of plates despite use of intravenous corticosteroids. A preliminary diagnosis was: infective endocarditis, pneumonia, erosive gastritis and duodenitis accompanied by anemia, leukocytosis and thrombocytopenia.The patient was then transferred to the Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia in Katowice. Physical examination revealed a heart murmur and splenomegaly. Blood test showed persistent anemia, decreased plateled count and hyperleukocytosis. A peripheral blood smear determined the presence of blasts.Ultrasound imaging of the abdomen revealed enlarged spleen (14.6x9.9 cm). Bone marrow aspirate confirmed the findings of blood smear and showed the presence more than 50% of myelomonoblastic cells. The flow cytometric immunophenotyping report indicated the malignant cells were positive for HLA-DR, MPO, CD13, CD15, CD33, CD116 and cytogenetic analysis showed the inv (16) (p13;q22). Molecular analysis of bone marrow cells using RT-PCR identified a CBFB-MYH11 fusion protein.Low cytogenetic risk patient was treated with individualized induction therapy DA: daunorubicin (60 mg/m2 on days 1–3) and cytosine arabinoside (200 mg/m2 on days 1–5). Hemodiadialyzotherapy was continued. His chemiotherapy- induced bone marrow aplasia with granulocytopenia was complicated by pneumonia.The patient achieved a complete hematologic remission in peripheral blood, but not molecular remission after induction chemotherapy (positive RT-PCR assays for oncogene CBFB-MYH11). The Patient then received consolidation treatment with HAM (mitoxantrone 10 mg/m2 on days 1–2 and cytosine arabinoside 1500 mg/m2 on days 1–5). During the period of profound aplasia an additional hemodialysis due to hyperkalemia was required. Prolonged bone marrow aplasia resulted in severe interstitial pneumonia and septicemia. Despite intensive therapeutic measures the patient died from respiratory failure.The autopsy revealed a pulmonary edema, massive hyperemia of the left lower lobe with pneumonia confluens.

      PatientID: 1

      KindredID: 1

      Case: M, 38Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: His father, uncle and grandmother were diagnosed with renal cell cancer but no genetic data is available.

      CasePresentingHPOs: HP:0001903; HP:0002090; HP:0005584; HP:0010797; HP:0000790; HP:0001644; HP:0010535; HP:0001654; HP:0005263; HP:0001873; HP:0001974; HP:0006689; HP:0033117; HP:0030148; HP:0001744; HP:0006515; HP:0100806; HP:0100598; HP:0100598; HP:0004930; HP:0004808 (Anemia, Pneumonia, Renal cell carcinoma, Hemangioblastoma, Hematuria, Dilated cardiomyopathy, Sleep apnea, Abnormal heart valve morphology, Gastritis, Thrombocytopenia, Leukocytosis, Bacterial endocarditis, Duodenitis, Heart murmur, Splenomegaly, Interstitial pneumonitis, Sepsis, Pulmonary edema, Abnormality of the pulmonary vasculature, Acute myeloid leukemia)

      CaseHPOFreeText: 38-year-old male patient diagnosed with von Hippel-Lindau disease in 2008 admitted with significant anemia, increased number of leukocytes, pneumonia and with suspected endocarditis. In June 2007 the patient underwent right nephrectomy for RCC and then in October 2007 he had surgery to remove a hemangioblastoma from his brainstem (medulla oblongata). In October 2010, he was diagnosed with a solitary kidney tumor (histologically confirmed RCC). Postoperative course was complicated by massive hematuria leading to urgent nephrectomy resulting in chronic hemodialysis. In March 2011, he was diagnosed with dilated cardiomyopathy and complex valves defect. In May 2011, severe central sleep apnea was determined. In July 2011, anemia, leukocytosis and moderate thrombocytopenia were determined. Gastroscopy revealed erosive gastritis. A preliminary diagnosis was made of infective endocarditis, pneumonia and duodenitis. Physical examination revealed a heart murmur and splenomegaly. Blood test showed persistent anemia, decreased platelet count and hyperleukocytosis. Ultrasound imaging of the abdomen revealed enlarged spleen. Prolonged bone marrow aplasia resulted in severe interstitial pneumonia and septicemia. The patient died from respiratory failure. The autopsy revealed a pulmonary edema, massive hyperemia of the left lower lobe with pneumonia confluens.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.F136S (c.407T>C)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Authors declare variant as: “407 C/T (F136S)”.

      ClinVarID: 496064, https://www.ncbi.nlm.nih.gov/clinvar/variation/496064/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: F136S (c.407T>C)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:hemangioblastoma DiseaseEntity:anemia DiseaseEntity:pneumonia DiseaseEntity:hematuria DiseaseEntity:dilatedcardiomyopathy DiseaseEntity:sleepapnea DiseaseEntity:abnormalheartvalvemorphology DiseaseEntity:gastritis DiseaseEntity:thrombocytopenia DiseaseEntity:leukocytosis DiseaseEntity:bacterialendocarditis DiseaseEntity:duodenitis DiseaseEntity:heartmurmur DiseaseEntity:splenomegaly DiseaseEntity:interstitialpneumonitis DiseaseEntity:sepsis DiseaseEntity:pulmonaryedema DiseaseEntity:abnormalityofthepulmonaryvasculature DiseaseEntity:acutemyeloidleukemia Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:407 ProteinPosition:136 AminoAcidChange:PHEtoSER ClinVarID:496064 ClinVarID:Yes MutationType:missense_variant;transition CivicName:F136S(c.407T>C) Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC3846582/