Genotype-phenotype correlations, and retinal function and structure in von Hippel-Lindau disease.

Abstract

PURPOSE:

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: Elisabeth Wittström, Margareta Nordling, Sten Andréasson
• Journal: Ophthalmic genetics (Ophthalmic Genet) Vol. 35 Issue 2 Pg. 91-106 (Jun 2014) ISSN: 1744-5094 [Electronic] England
• PMID: 24555745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Von Hippel-Lindau Tumor Suppressor Protein
• VHL protein, human

Topics

• Adolescent
• Adrenal Gland Neoplasms (genetics, physiopathology, surgery)
• Adult
• Aged
• Carcinoma, Renal Cell (genetics, physiopathology, surgery)
• Cerebellar Neoplasms (genetics, physiopathology, surgery)
• DNA Mutational Analysis
• Electroretinography
• Female
• Genetic Association Studies
• Hemangioblastoma (genetics, physiopathology, surgery)
• Humans
• Kidney Neoplasms (genetics, physiopathology, surgery)
• Male
• Middle Aged
• Mutation, Missense
• Pedigree
• Pheochromocytoma (genetics, physiopathology, surgery)
• Retina (physiopathology)
• Retinal Neoplasms (genetics, physiopathology, surgery)
• Tomography, Optical Coherence
• Von Hippel-Lindau Tumor Suppressor Protein (genetics)
• Young Adult
• von Hippel-Lindau Disease (genetics, physiopathology)