Genotype-phenotype correlations, and retinal function and structure in von Hippel-Lindau disease.
Ophthalmic Genet
; 35(2): 91-106, 2014 Jun.
Article
en En
| MEDLINE
| ID: mdl-24555745
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Retina
/
Estudios de Asociación Genética
/
Enfermedad de von Hippel-Lindau
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Ophthalmic Genet
Asunto de la revista:
GENETICA MEDICA
/
OFTALMOLOGIA
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Reino Unido