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Genotype-phenotype Correlations, and Retinal Function and Structure in von Hippel-Lindau Disease.

Wittström, Elisabeth LU ; Nordling, Margareta and Andréasson, Sten LU (2014) In Ophthalmic Genetics 35(2). p.91-106
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Ophthalmic Genetics
volume
35
issue
2
pages
91 - 106
publisher
Taylor & Francis
external identifiers
  • pmid:24555745
  • wos:000335923100006
  • scopus:84899874656
ISSN
1744-5094
DOI
10.3109/13816810.2014.886265
language
English
LU publication?
yes
id
036adbab-5d17-4179-9802-b6996970a037 (old id 4334364)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24555745?dopt=Abstract
date added to LUP
2014-03-05 21:03:13
date last changed
2017-11-19 03:09:35
@article{036adbab-5d17-4179-9802-b6996970a037,
  abstract     = {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.},
  author       = {Wittström, Elisabeth and Nordling, Margareta and Andréasson, Sten},
  issn         = {1744-5094},
  language     = {eng},
  number       = {2},
  pages        = {91--106},
  publisher    = {Taylor & Francis},
  series       = {Ophthalmic Genetics},
  title        = {Genotype-phenotype Correlations, and Retinal Function and Structure in von Hippel-Lindau Disease.},
  url          = {http://dx.doi.org/10.3109/13816810.2014.886265},
  volume       = {35},
  year         = {2014},
}