title: Genotype-phenotype correlations, and retinal function and structure in von Hippel-Lindau disease.
abstract: OBJECTIVE
  To investigate genotype-phenotype correlation and to analyze functional and structural changes in the retina of patients with von Hippel-Lindau (VHL) disease.
  
  
  METHODS
  Thirteen patients from four families (A, B, C and D) with known VHL disease and known mutations in the VHL gene were examined. All patients underwent clinical examination and optical coherence tomography (OCT). Full-field electroretinography (full-field ERG) was performed in twelve patients.
  
  
  RESULTS
  Family A, with deletion of exon 3 in the VHL gene, and family B, with the missense mutation p.R79P, exhibited type 1 VHL characterized by the absence of pheochromocytoma and a high incidence of central nervous system hemangioblastomas. One member of family B exhibited Goldenhar syndrome. A novel missense mutation (p.L198P) was identified in the VHL gene in the patient from family C. This p.L198P mutation caused a phenotype with early onset of a neuroendocrine tumor of the pancreas, bilateral pheochromocytomas, and optic nerve hemangioblastoma. Full-field ERG showed significantly prolonged implicit times of the b-wave and maximal combined a-wave in VHL patients, compared to controls. Examination of the retinal structure in all patients with VHL, using OCT, showed a significant decrease in retinal thickness in VHL patients without ocular hemangioblastomas, compared to controls.
  
  
  CONCLUSIONS
  Our findings support previously established genotype-phenotype correlations. However, we here describe an unusual phenotype with a novel missense mutation, p.L198P, and report the finding that VHL disease can be associated with Goldenhar syndrome. Electrophysiological and structural findings suggest that VHL disease is a progressive, neurodegenerative disease of the retina.
authors.affiliation: Department of Ophthalmology, Lund University , Sweden and.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wittström
authors.forename: Margareta
authors.initials: M
authors.lastname: Nordling
authors.forename: Sten
authors.initials: S
authors.lastname: Andréasson
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D056726:Genetic Association Studies; D018325:Hemangioblastoma / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D012160:Retina / Q000503:physiopathology*; D019572:Retinal Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D041623:Tomography, Optical Coherence; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000235:genetics / Q000503:physiopathology*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human