Systematic screening of BEST1 and PRPH2 in juvenile and adult vitelliform macular dystrophies: a rationale for molecular analysis.
OBJECTIVE
To evaluate a genetic approach of BEST1 and PRPH2 screening according to age of onset, family history, and Arden ratio in patients with juvenile vitelliform macular dystrophy (VMD2) or adult-onset vitelliform macular dystrophy (AVMD), which are characterized by autofluorescent deposits.


METHODS
Clinical, electrophysiologic, and molecular retrospective study.


METHODS
The database of a clinic specialized in genetic sensory diseases was screened for patients with macular vitelliform dystrophy. Patients with an age of onset less than 40 years were included in the VMD2 group (25 unrelated patients), and patients with an age of onset more than 40 years were included in the AVMD group (19 unrelated patients).


METHODS
Clinical, fundus photography, and electro-oculogram (EOG) findings were reviewed. Mutation screening of BEST1 and PRPH2 genes was systematically performed.


METHODS
Relevance of age of onset, family history, and Arden ratio were reviewed.


RESULTS
Patients with VMD2 carried a BEST1 mutation in 60% of the cases. Seven novel mutations in BEST1 (p.V9L, p.F80V, p.I73V, p.R130S, pF298C, pD302A, and p.179delN) were found. Patients with VMD2 with a positive family history or a reduced Arden ratio carried a BEST1 mutation in 70.5% of cases and in 83% if both criteria were fulfilled. Patients with AVMD carried a PRPH2 mutation in 10.5% of cases and did not carry a BEST1 mutation. The probability of finding a PRPH2 mutation increased in the case of a family history (2/5 patients). Electro-oculogram was normal in 3 of 15 patients with BEST1 mutations and reduced in the 3 patients with PRPH2 mutations.


CONCLUSIONS
Age of onset is a major criterion to distinguish VMD2 from AVMD. Electro-oculogram is not as relevant because decreased or normal Arden ratios have been associated with mutations in both genes and diseases. A positive family history increased the probability of finding a mutation. BEST1 screening should be recommended to patients with an age of onset less than 40 years, and PRPH2 screening should be recommended to patients with an age of onset more than 40 years. For an onset between 30 and 40 years, PRPH2 can be screened if no mutation has been detected in BEST1.


BACKGROUND
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France. isabelannemeunier@yahoo.fr
Isabelle
I
Meunier
Audrey
A
Sénéchal
Claire-Marie
CM
Dhaenens
Carl
C
Arndt
Bernard
B
Puech
Sabine
S
Defoort-Dhellemmes
Gaël
G
Manes
Delphine
D
Chazalette
Emilie
E
Mazoir
Béatrice
B
Bocquet
Christian P
CP
Hamel
D000328:Adult; D000368:Aged; D000075002:Bestrophins; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005820:Genetic Testing; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D064531:Peripherins; D012189:Retrospective Studies; D057826:Vitelliform Macular Dystrophy / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578997:PRPH2 protein, human; D064531:Peripherins; D004247:DNA