BEST1 mutations in Japanese patients with Best vitelliform macular dystrophy

Abstract

 

Purpose

 

To report BEST1 mutations in Japanese patients with Best vitelliform macular dystrophy (BVMD).

 

Methods

 

A total of 18 BVMD patients in 13 Japanese families were recruited in this study. We performed ophthalmic examinations, including decimal best-corrected visual acuity, slit-lamp biomicroscopy, dilated funduscopy, optical coherence tomography, full-field electroretinography, and electrooculography. Genomic DNA samples were obtained and analyzed for mutations in the BEST1 gene by Sanger sequencing.

 

Results

 

Twelve different BEST1 mutations were identified in the 13 BVMD probands. Ten mutations [c.4A>G (p.T2A), c.73C>T (p.R25W), c.240C>A(p.F80L), c.241G>A (p.V81M), c.584C>T (p.A195V), c.653G>A (p.R218H), c.665G>A (p.G222E), c.724G>A (p.V242M), c.910_912delGAT (p.D304del), c.918G>C (p.Q306N)] have been described in the literature, while 2 mutations [c.20g/a (p.S7N), c.1037C>A (p.P346H)] were novel. Compound heterozygous mutations (p.S7N and p.R218H) were found in one family. The phenotypes of almost all probands showed either stage of typical BVMD; fundus appearance, normal ERG, and abnormal EOG. Only one patient with the p.A195V mutation showed decreased ERG.

 

Conclusions

 

Twelve mutations in the BEST1 gene were identified in the 13 families with BVMD and 2 (p.S7N and p.P346H) of those mutations were novel. One patient had compound heterozygous mutations (p.S7N and p.R218H) but exhibited a typical phenotype of BVMD. Although variable BEST1 mutations were identified in this study of Japanese origin, particular frequent mutation was not found. To date, there is no report of BEST1 mutational analysis in considerable Japanese patients. Our results suggest that BEST1 mutations are largely involved in Japanese BVMD patients.

 

 

Keywords: 696 retinal degenerations: hereditary • 537 gene screening