Molecular characterization and ophthalmic investigation of a large family with type 2A Von Hippel-Lindau Disease

Richard C Allen; Andrew R Webster; Ruifang Sui; Jeremiah Brown; Christine M Taylor; Edwin M Stone

doi:10.1001/archopht.119.11.1659

Back

Molecular characterization and ophthalmic investigation of a large family with type 2A Von Hippel-Lindau Disease

Journal article

Open access

Peer reviewed

Molecular characterization and ophthalmic investigation of a large family with type 2A Von Hippel-Lindau Disease

Richard C Allen, Andrew R Webster, Ruifang Sui, Jeremiah Brown, Christine M Taylor and Edwin M Stone

Archives of ophthalmology (1960), Vol.119(11), pp.1659-1665

11/2001

DOI: 10.1001/archopht.119.11.1659

PMID: 11709017

Files and links (1)

url

https://doi.org/10.1001/archopht.119.11.1659View

Published (Version of record) Open Access

Abstract

Von Hippel-Lindau (VHL) disease is a dominantly inherited cancer syndrome. Since the identification of the VHL gene, at least 3 clinical-genetic subtypes of the disease have been recognized. To identify the specific abnormality in the VHL gene and to correlate it with the prevalence and severity of ocular involvement in a large family with VHL disease. A longitudinal clinical study and DNA analysis of 24 family members. All 14 affected family members exhibited a thymine-to-cysteine change at nucleotide 505 (T505C) in exon 1 of the VHL gene, consistent with the clinical diagnosis of VHL disease subtype 2A. Two asymptomatic gene carriers were also identified. Seventy-five percent (12/16) of the gene carriers had 1 or more ocular angiomas. The mean number of ocular angiomas per gene carrier was 3.3. Six eyes had optic disc angioma. Five gene carriers (31%) had lost vision because of angiomatosis. Cerebellar hemangioblastomas were present in 4 patients (25%) and pheochromocytomas in 11 (69%). No patient was found to have a renal cell carcinoma. The family shows a low susceptibility to renal carcinoma consistent with the clinical diagnosis of VHL disease type 2A. The prevalence and severity of ocular angiomatosis in this subtype do not significantly differ from those of the other more common subtypes of VHL. Recognition of the VHL disease 2A phenotype suggests the presence of a specific mutation (T505C) in the VHL gene. Confirmation of this genotype increases the clinician's ability to provide favorable prognostic information to affected family members.

Phenotype

Polymerase Chain Reaction

Humans

Ligases - genetics

Middle Aged

Male

von Hippel-Lindau Disease - classification

DNA Primers - chemistry

von Hippel-Lindau Disease - diagnosis

Adrenal Gland Neoplasms - diagnosis

Retinal Neoplasms - diagnosis

DNA Mutational Analysis

Germ-Line Mutation

Adult

Female

Genes, Tumor Suppressor

Hemangioma - genetics

Pheochromocytoma - diagnosis

Brain Neoplasms - diagnosis

Brain Neoplasms - genetics

Genotype

von Hippel-Lindau Disease - genetics

Hemangioma - diagnosis

Ubiquitin-Protein Ligases

Point Mutation

Pedigree

Pheochromocytoma - genetics

Aged

Von Hippel-Lindau Tumor Suppressor Protein

Adrenal Gland Neoplasms - genetics

Retinal Neoplasms - genetics

Tumor Suppressor Proteins

Details

Title: Subtitle: Molecular characterization and ophthalmic investigation of a large family with type 2A Von Hippel-Lindau Disease
Creators: Richard C Allen - Department of Ophthalmology and Visual Sciences, The University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242, USA
Andrew R Webster
Ruifang Sui
Jeremiah Brown
Christine M Taylor
Edwin M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.119(11), pp.1659-1665
DOI: 10.1001/archopht.119.11.1659
PMID: 11709017
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Language: English
Date published: 11/2001
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980084202771

Metrics

12 Record Views

9 Times Cited - Web of Science