Course of visual decline in relation to the Best1 genotype in vitelliform macular dystrophy.
OBJECTIVE
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.


METHODS
Consecutive case series.


METHODS
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.


METHODS
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: 2-78). 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 phenotype-genotype correlation, because the Ala10Val mutation has a more rapid disease progression than other common mutations.


BACKGROUND
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Booij
Judith C
JC
Department of Clinical and Molecular Ophthalmogenetics, the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Boon
Camiel J F
CJ
van Schooneveld
Mary J
MJ
ten Brink
Jacoline B
JB
Bakker
Arne
A
de Jong
Paulus T V M
PT
Hoyng
Carel B
CB
Bergen
Arthur A B
AA
Klaver
Caroline C W
CC
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000075002:Bestrophins; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004585:Electrooculography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D014786:Vision Disorders / Q000503:physiopathology*; D014792:Visual Acuity / Q000502:physiology*
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins