Elsevier

Ophthalmology

Volume 118, Issue 6, June 2011, Pages 1130-1136
Ophthalmology

Original article
Systematic Screening of BEST1 and PRPH2 in Juvenile and Adult Vitelliform Macular Dystrophies: A Rationale for Molecular Analysis

Presented as a poster at: the American Academy of Ophthalmology, Annual Meeting, October 26–27, 2009, San Francisco, California.
https://doi.org/10.1016/j.ophtha.2010.10.010Get rights and content

Purpose

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.

Design

Clinical, electrophysiologic, and molecular retrospective study.

Participants

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.

Main Outcome Measures

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.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Patients and Methods

The database of the outpatient clinic for genetic sensory diseases, Maolya (Montpellier University Hospital, France), was screened for families with presumed VMD2 and AVMD. Informed consent was obtained for clinical examination and genetic analysis from all patients, according to approved protocols of the Montpellier University Hospital, in agreement with the Declaration of Helsinki.

Results

From 1990 to 2009, among the 1585 families included in the Maolya database of the outpatient clinic for genetic sensory diseases, 279 families had a macular dystrophy (17.6%). Within this subgroup, 25 unrelated patients were classified with VMD2 disease (8.9%) and 19 were classified with AMVD (6.8%).

Discussion

The present study was designed to evaluate the relevance of age of onset, Arden ratio, and family history in VMD2 and AVMD, and to propose a rationale for genetic screening. Age of onset was the best criterion to predict the presence of a mutation in either BEST1 or PRPH2. Electro-oculogram Arden ratio was not as relevant as previously thought because 20% of BEST1-positive patients had a normal ratio and the 3 PRPH2-positive patients had a decreased ratio. Nevertheless, a positive family

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    Manuscript no. 2010-499.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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