Objective: To examine the clinical phenotype of three Swedish families with Best's vitelliform macular dystrophy (BMD) and three different mutations in the recently identified bestrophin gene.
Methods: Three families, including 13 patients, were examined clinically using visual acuity testing, electro-oculography, fundus inspection, and fundus photography. The mutations were previously determined by direct sequence analysis of the individual exons in the bestrophin gene.
Results: The largest family (SL76), with the Y85K (T357C) mutation in the bestrophin gene, demonstrated a clinical phenotype characterized by a variable degree of visual acuity reduction and a marked intrafamilial variability in macular pathology. The electro-oculograms, however, demonstrated similar results in all patients regardless of the severity of the macular dysfunction. The smallest family (SL3), with the mutation V9A (T130C) in the bestrophin gene, and the family (SL2) with the mutation D104E (C416A) demonstrated a similar clinical phenotype. The majority of patients (11/13 examined subjects) had a binocular visual acuity of 20/63 or better at a late stage of the disease course, indicating a relatively good prognosis for visual acuity in this specific phenotype. The ophthalmoscopic changes were followed in one of the patients for 38 years and in three of the patients for 19 years and showed that the macular appearance seems to be stable after adolescence.
Conclusions: Patients with BMD and mutations in the bestrophin gene have a similar clinical phenotype characterized by a variable, but relatively moderate visual acuity reduction, atrophic changes in the macula, and pathological results of the electro-oculograms. The macular appearance remains essentially unchanged through the atrophic stage (stage IV) in the majority of patients, indicating a stationary disease course associated with this specific genotype.