The proband was a 28-year-old male, who presented with an episodic headache for 10 years. Both the finger-nose test and the Romberg's sign were recorded as positive in the physical examination. A cyst and a nodule were revealed via brain MRI (Fig. 2). The cyst was demonstrated to be a hemangioblastoma tumor following surgical excision followed by histopathological analysis of the biopsy tissues. H&E staining revealed that the lesion contained a large number of thin-walled capillaries (Fig. 3). The sole neoplastic element, known as the ‘stromal cell’, inhabited the interstices between ramifying vascular arcades. Stromal cells stained for S-100 and NSE exhibited dense-core intracytoplasmic granules, however did not demonstrate expression of GFAP or EMA (Fig. 3), which has previously been detected immunohistochemically in most nonneoplastic epithelia (18). Stromal cells did not exhibit positive staining for endothelial markers such as CD34, whereas the thin-walled capillaries were positive; stromal cells occasionally exhibited the expression of vascular marker F8 (Fig. 3). The expression of Ki-67, which is a proliferation marker (19), was <1% (Range of normal value 1–2%; Fig. 3). Therefore, the proband was diagnosed with VHL syndrome at the Hunan Cancer Hospital (Changsha, China).
PatientID: proband (III:2)
KindredID: 1
Case: M, 28Y0M, Chinese
DiseaseAssertion: VHL
FamilyInfo: Two of the proband's maternal cousins were healthy individuals that were demonstrated to carry the same mutation, as revealed by Sanger sequencing: III:4, male, and III:8, female as seen in the pedigree from Figure 1. A further five affected members of the family had previously died from this syndrome, including the proband's mother (II:2), maternal grandfather (I:1), two uncles (II:3 and II:5), and a cousin (III:10). These deceased family members had not previously been tested for mutations in the VHL gene. Pedigree: see Figure 1.
CasePresentingHPOs: HP:0010797 (Hemangioblastoma)
CaseHPOFreeText: A cyst and a nodule were revealed via brain MRI. The cyst was demonstrated to be a hemangioblastoma tumor following surgical excision
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: NA
SupplementalData: NA
Variant: p.H115Q (c.345C>A)
ClinVar: 496057 https://www.ncbi.nlm.nih.gov/clinvar/variation/496057/
CAID:N/A
gnomAD: N/A
VariantEvidence: RNA extracted from peripheral blood samples obtained from patients in the pedigree and the healthy controls. No significant difference in the expression of pVHL was demonstrated between the mutated and wild type cDNA, as demonstrated by RT-sqPCR analysis.
MutationType: missense_variant;transversion
CivicName: H115Q (c.345C>A)
MultipleGeneVariants: N/A