Clinical and genetic heterogeneity in multifocal vitelliform dystrophy.
OBJECTIVE
To describe the clinical and genetic findings in 15 patients with multifocal vitelliform lesions.


METHODS
All patients and, if possible, affected family members underwent an ophthalmic examination and their genomic DNA was analyzed for mutations in the vitelliform macular dystrophy 2 (VMD2) gene. Patients who did not have a mutation in the VMD2 gene were screened for mutations in the peripherin/RDS gene.


RESULTS
Patient age at onset of the disease was highly variable, ranging from 5 to 59 years. The peripheral lesions varied in number, size, and overall appearance but showed similar characteristics at autofluorescence imaging and optical coherence tomography compared with the central vitelliform lesion. Mutations in the VMD2 gene were identified in 9 of 15 patients. One patient without a VMD2 mutation carried a sequence variant in the 5' untranslated region of the peripherin/RDS gene.


CONCLUSIONS
Multifocal vitelliform dystrophy is a clinically and genetically heterogeneous retinal disease that can be caused by mutations in the VMD2 gene. Other genes associated with this phenotype remain to be identified.


CONCLUSIONS
Clinical and molecular genetic characterization of multifocal vitelliform dystrophy may lead to better understanding of the pathophysiological mechanisms underlying this phenotype and may enable a more accurate prognosis in individual patients.
Boon
Camiel J F
CJ
Department of Ophthalmology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands.
Klevering
B Jeroen
BJ
den Hollander
Anneke I
AI
Zonneveld
Marijke N
MN
Theelen
Thomas
T
Cremers
Frans P M
FP
Hoyng
Carel B
CB
D000293:Adolescent; D000328:Adult; D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D004585:Electrooculography; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009887:Ophthalmoscopy; D064531:Peripherins; D010857:Pigment Epithelium of Eye / Q000473:pathology*; D016133:Polymerase Chain Reaction; D049268:Positron-Emission Tomography; D011379:Prognosis; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D014792:Visual Acuity
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D004247:DNA