Original articleCourse of Visual Decline in Relation to the Best1 Genotype in Vitelliform Macular Dystrophy
Section snippets
Study Population
Patients with a clinical and molecular diagnosis of VMD who presented to 3 specialized ophthalmogenetic clinics in the Netherlands between 2003 and 2007 were considered eligible for inclusion in the study. The clinical and molecular diagnosis included a VMD lesion in the retina (see below) and the presence of a disease-causing mutation in the Best1 gene. Exclusion criteria were uncertain with regard to the clinical diagnosis or the absence of a disease-causing mutation. Twenty-nine probands and
Clinical Characteristics at First Presentation
Demographic data of all 53 patients are presented in Table 1. The patients were genealogically linked to 27 pedigrees; 16 individuals were sporadic patients and 37 individuals had at least 1 relative with a VMD phenotype. The study population consisted of 29 male and 24 female patients.
The age at the first visit to an ophthalmologist ranged from age 2 to 78 years, with a median of 33 years. Seventeen patients had an early onset (<10 years of age), 18 patients had an onset during age 10 to 18
Discussion
We show that VMD, caused by mutations in the Best1 gene, is a disease with a variable age of onset and clinical course, ultimately leading to visual decline. Our survival analyses indicate that the variability may in part be explained by differences in genotype. Vision in the majority of patients deteriorated to such an extent that driving was prohibited at middle age and that reading was generally compromised after age 70 years. However, development of legal blindness was rare, even at higher
References (32)
- et al.
Long-term evaluation of patients with Best's vitelliform dystrophy
Ophthalmology
(1981) - et al.
The spectrum of ocular phenotypes caused by mutations in the BEST1 gene
Prog Retin Eye Res
(2009) - et al.
Phenotype and genotype correlations in two Best families
Ophthalmology
(2003) - et al.
Insertion and topology of normal and mutant bestrophin-1 in the endoplasmic reticulum membrane
J Biol Chem
(2007) - et al.
Structure-function analysis of the bestrophin family of anion channels
J Biol Chem
(2003) - et al.
Fundus autofluorescence imaging of retinal dystrophies
Vision Res
(2008) - et al.
The gene for Best's macular dystrophy is located at 11q13 in a Swedish family
Clin Genet
(1992) - et al.
Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13
Nat Genet
(1992) - et al.
Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease)
Hum Mol Genet
(1998) - et al.
Identification of the gene responsible for Best macular dystrophy
Nat Genet
(1998)
VMD2 and its role in Best's disease and other retinopathies [in German]
Ophthalmologe
Molecular physiology of bestrophins: multifunctional membrane proteins linked to Best disease and other retinopathies
Physiol Rev
Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium
Proc Natl Acad Sci U S A
The vitelliform macular dystrophy protein defines a new family of chloride channels
Proc Natl Acad Sci U S A
Regulation of bestrophin Cl channels by calcium: role of the C terminus
J Gen Physiol
The anion-selective pore of the bestrophins, a family of chloride channels associated with retinal degeneration
J Neurosci
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Manuscript no. 2009-709.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.