Clinical and genetic findings of autosomal recessive bestrophinopathy in Japanese cohort

Abstract Purpose To report the clinical and genetic findings of 9 Japanese patients with autosomal recessive bestrophinopathy (ARB). Design Retrospective, multicenter observational case series. Methods Nine ARB patients from 7 unrelated Japanese families that were examined in 3 institutions in Japan were studied. A series of ophthalmic examinations including fundus photography, spectral domain optical coherence tomography, fundus autofluorescence, electrooculography (EOG), electroretinography, and the results of genetic analysis were reviewed. Results Genetic analyses identified 7 pathogenic variants in BEST1 including 2 novel variants, c.478G>C (p.A160P) and c.948+1delG. Homozygous variants were found in 4 families and compound heterozygous variants were found in 3 families. Two patients were diagnosed as ARB only after the whole exome sequencing analyses. The Arden ratio of the EOG was less than 1.5 in all 7 patients tested. Vitelliform lesions typical for BVMD were not seen in any of the patients. Seven patients shared some of the previously described features of ARB; subretinal deposits, extensive subretinal fluid, and cystoid macular edema (CME). However, the other two patients with severe retinal degeneration lacked these features. Focal choroidal excavations were present bilaterally in two patients. One case had a marked reduction of the CME and expansion of subretinal deposits over an 8 year of follow-up period. Conclusions Japanese ARB patients had some but not all of the previously described features. Genetic analyses are essential to diagnose ARB correctly in consequence of considerable phenotypic variations.