Purpose: To describe the disease course in patients with vitelliform macular dystrophy (VMD) with a Best1 mutation and to determine the association between Best1 genotype and visual prognosis. Design: Consecutive case series. Participants: Fifty-three patients with VMD with Best1 mutations from 27 Dutch families, aged 11 to 87 years. Methods: Best-corrected visual acuity (VA), fundus appearance, and Arden ratio on the electro-oculogram (EOG) during clinical follow-up were assessed from medical records. Mutation analysis of the Best1 gene was performed on DNA samples using denaturing high-pressure liquid chromatography and direct sequencing. Main Outcome Measures: Cumulative lifetime risk of visual decline below 0.5, 0.3, and 0.1 for the entire group and stratified for genotype. Results: Median age of onset of visual symptoms was 33 years (range: 278). The cumulative risk of VA below 0.5 (20/40) was 50% at 55 years and 75% at 66 years. The cumulative risk of decline less than 0.3 (20/63) was 50% by age 66 years and 75% by age 74 years. Two patients progressed to VA less than 0.1 (20/200). Fourteen different mutations were found. Most patients (96%) had missense mutations; the Thr6Pro, Ala10Val, and Tyr227Asn mutations were most common. Visual decline was significantly faster in patients with an Ala10Val mutation than either the Thr6Pro or the Tyr227Asn mutation (P=0.001). Conclusions: Age of onset of visual symptoms varies greatly among patients with VMD. All patients show a gradual decrease in VA, and most progress to visual impairment at a relatively late age. Our data suggest a phenotypegenotype correlation, because the Ala10Val mutation has a more rapid disease progression than other common mutations. © 2010 by the American Academy of Ophthalmology.

adolescent, adult, aged, alanine, article, asparagine, best1 gene, child, clinical feature, controlled study, denaturing high performance liquid chromatography, disease course, electrooculogram, female, gene, gene mutation, genotype phenotype correlation, human, major clinical study, male, medical assessment, medical record, missense mutation, mutational analysis, nucleotide sequence, priority journal, prognosis, proline, retina macula vitelliform degeneration, risk factor, school child, threonine, tyrosine, valine, visual acuity
dx.doi.org/10.1016/j.ophtha.2009.11.044, hdl.handle.net/1765/20661
Erasmus MC: University Medical Center Rotterdam

Booij, J.C, Boon, C.J.F, Schooneveld, M.J, ten Brink, J.B, Bakker, A, de Jong, P.T.V.M, … Klaver, C.C.W. (2010). Course of visual decline in relation to the best1 genotype in vitelliform macular dystrophy. Ophthalmology, 117(7), 1415–1422. doi:10.1016/j.ophtha.2009.11.044