Elsevier

Ophthalmology

Volume 110, Issue 9, September 2003, Pages 1724-1731
Ophthalmology

Original article
Phenotype and genotype correlations in two best families

https://doi.org/10.1016/S0161-6420(03)00575-XGet rights and content

Abstract

Objective

To evaluate mutations in the Best mascular dystrophy (VMD2) gene in two families with Best disease and to describe the phenotype–genotype correlations of genetically determined affected and unaffected individuals.

Design

Family genetic study.

Participants

Two families with Best disease were identified, and family members were evaluated by ophthalmologic examination or fundus photography to assess their phenotype. All affected patients and some of the unaffected family members had a blood sample drawn, and the DNA was analyzed for mutations in the VMD2 gene.

Main outcome measures

Twenty-one subjects in the two pedigrees with Best disease were studied. One amino acid-changing mutation in the VMD2 gene was found to segregate independently in each family (P297S or E300D, respectively).

Results

Eleven individuals had some evidence of maculopathy, including retinal pigment epithelial changes, drusen, pigment epithelial irregularities, or cicatricial changes. Ten of these 11 patients (91%) with maculopathy had a mutation in the VMD2 gene, of whom 8 were clinically diagnosed as having Best disease and 2 were diagnosed as having possible Best maculopathy. The one patient without a mutation in the VMD2 gene had age-related macular degeneration (AMD). Ten family members did not have evidence of maculopathy, of whom 6 had no mutation in the VMD2 gene. Four family members (2 in each pedigree) had mutations in the VMD2 gene, abnormal electro-oculogram (EOG) results, but normal maculae at age 40 or older. Of the 7 individuals with no mutation in the VMD2 gene, 6 were phenotypically normal and the other had late-onset visual loss resulting from AMD.

Conclusions

All family members with maculopathy consistent with Best disease (n = 10) had an amino acid-changing mutation in the VMD2 gene. Four individuals who did not have maculopathy, but did have an abnormal EOG, also had mutations in the VMD2 gene. The presence of a VMD2 mutation is associated with abnormal retinal function, which can occur in the absence of phenotypic manifestation of macular disease.

Section snippets

Methods

The Family Macular Degeneration Study at the Epidemiology Unit of the Massachusetts Eye and Ear Infirmary is a National Institutes of Health-supported, Human Subjects Committee-approved study for evaluation of the genetic basis of macular degeneration. From this study's database, we identified two families with a maculopathy diagnosed as Best disease. One member of each family underwent genotyping to serve as an internal control for Best disease in a study of non-Best maculopathies.10 Cases of

Results

Twenty-one family members in the two pedigrees were studied (Table 1). Eleven individuals had some evidence of maculopathy within a 1500μ diameter circle centered on the fovea, and no eccentric lesions were seen. Ten of these 11 patients (91%) with maculopathy had a mutation in the VMD2 gene, of which 8 were clinically diagnosed as Best disease and 2 were consistent with Best maculopathy. The one patient with maculopathy who did not have a mutation in the VMD2 gene had AMD. Ten family members

Discussion

Ten of 11 patients with maculopathy in the two pedigrees had mutations in the VMD2 gene. These 10 family members had either juvenile- or adult-onset visual loss with funduscopic findings consistent with Best disease. The one patient with maculopathy who did not have a mutation in this gene had late-onset visual loss and findings consistent with exudative AMD. The four asymptomatic individuals who lacked demonstrable pathologic features in the macula on funduscopic examination but had abnormal

Acknowledgements

The authors thank the families who participated in this study, as well as the ophthalmologists and optometrists who assisted with completing the study materials. These physicians include: William Deegan, MD, Samuel Gold, MD, Antonino Iorfino, MD, Sulayman Jallow, MD, Lawrence T. Reese, MD, George Shaker, MD, Robert Sherman, MD, Jack Sipperley, MD, Robert Stephens, MD, Lawrence Weene, MD, Gus Garmizo, OD, Michael J. Elman, MD, and Emily Chew, MD.

References (16)

There are more references available in the full text version of this article.

Cited by (0)

Manuscript no. 220491.

Supported by the National Institutes of Health, Bethesda, Maryland (grant nos.: EY 11309 and EY 13435); The Foundation Fighting Blindness, Inc., Owings Mills, Maryland; Massachusetts Lions Eye Research Fund, Inc., Northboro, Massachusetts; and Research to Prevent Blindness, Inc., New York, New York.

View full text