Clinical and molecular genetic analysis of best vitelliform macular dystrophy.
OBJECTIVE
To describe the phenotype of Best vitelliform macular dystrophy (BVMD) and to evaluate genotype-phenotype and histopathologic correlations.


METHODS
Retrospective analysis of patients with BVMD who underwent an extensive ophthalmic examination, including best-corrected Snellen visual acuity, fundus examination by indirect ophthalmoscopy, fundus photography, fundus autofluorescence, optical coherence tomography, fundus fluorescein angiography, and electrooculography. In addition, molecular genetic analysis of the BEST1 gene was performed in all patients.


RESULTS
We examined 40 eyes of 20 patients with BVMD. Sixteen eyes (40%) had a well-defined BVMD stage, whereas 18 eyes displayed characteristics attributable to different stages. Six eyes had an atypical form of BVMD. Fundus autofluorescence and optical coherence tomography frequently detected abnormalities that were not visible on ophthalmoscopy. All patients carried a mutation in the BEST1 gene. Molecular genetic analysis identified 8 different BEST1 mutations in 15 families, including 2 novel mutations (p.Gly299Ala and p.Ile3Thr). Genotype-phenotype correlation was limited, as we observed a broad phenotypic range in association with a single BEST1 mutation. However, the p.Ala243Val seems to cause a mild and relatively invariable BVMD phenotype.


CONCLUSIONS
A broad phenotypic variability may be observed in BVMD, even with a single BEST1 mutation. Fundus autofluorescence and optical coherence tomography are valuable noninvasive imaging techniques for phenotyping and follow-up of BVMD patients.
Department of Ophthalmology, Radboud University Nijmegen Medical Centre, The Netherlands. C.Boon@ohk.umcn.nl
Camiel J F
CJ
Boon
Thomas
T
Theelen
Elisabeth H
EH
Hoefsloot
Mary J
MJ
van Schooneveld
Jan E E
JE
Keunen
Frans P M
FP
Cremers
B Jeroen
BJ
Klevering
Carel B
CB
Hoyng
D000293:Adolescent; D000328:Adult; D000075002:Bestrophins; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D004585:Electrooculography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D009887:Ophthalmoscopy; D010641:Phenotype; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins