Abstract
Abstract: :
Purpose: To determine the phenotypic variability in patients with different mutations in the VMD2 (bestrophin) gene and to evaluate changes in fundus autofluorescence over time. Methods: Eight patients and four possible carriers of six unrelated families with Best disease (aged 6 to 57 years) were characterised by clinical examination, electrophysiology (EOG and multifocal ERG), fundus autofluorescence (AF) and molecular genetics. Results: Heterozygous mutations were found in all six families. Mutation I295del caused typical round lesions of 600–2400mm diameter in three unrelated 6 to 12 year old boys. The oldest boy had some scarring OD, the 8y old had only unilateral manifestation. The size of the lesion did not change significantly during 4 years of follow–up, the inner structure only slightly. The N99K mutation caused a similar fundus and AF aspect in a 6 y old boy during 5 years of follow–up. Two individuals with I295del (10 and 37 y, f) and two with N99K (13 and 37 y, f) were asymptomatic carriers identified during family examination with normal VA, fundus (except for slightly increased RPE–irregularities) and AF and no changes during 4 years follow–up. Lesions caused by R218L (16y, m) and I232N mutations (15y, f) showed a more irregular AF aspect with symptomatic vision loss. A 30 y old female with a T237S mutation had bilateral scarring and vision loss. Her two children aged 2 (m) and 4 (f) were clinically affected. A Y227F mutation in a 57 year old male caused the latest onset with a more irregular shape of the lesion. All individuals with mutations in VMD2 had reduced Arden–ratio in EOG, mfERG was reduced centrally in individuals with vision loss. Conclusions: Best disease is known to have variable penetrance and expressivity. In the present series the size of the lesions was not correlated with the mutation or with visual acuity (VA). Asymptomatic carriers were found with I295del and N99K mutations. Patients with mutations N99K, R218L, T237S and I232N were more severely affected than patients with I295del andY227F mutations, however patients with I295del mutations were still young. Lower VA corresponded to a more irregular pattern of increased AF within the lesion due to scarring or haemorrhage. The size of the lesions did not change significantly during 4 to 5 years of follow–up.
Keywords: retinal degenerations: hereditary • mutations • imaging/image analysis: clinical