Paradoxical autosomal recessive bestrophinopathy-like phenotypes shown in an autosomal dominant pedigree

This study aimed to evaluate the clinical and genetic characteristics of eight members from a Chinese Han family who displayed autosomal recessive bestrophinopathy (ARB)-like retinal changes in autosomal dominant (AD) inheritance pattern.

Clinical investigations included slit-lamp, tonometry, fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, electrooculography, and ultrasound biomicroscopy. Ocular axial length measurements were collected retrospectively. The targeted exome sequencing (TES) was applied for the genetic analysis of the proband. PCR-based Sanger sequencing was performed on the family for validation and co-segregation analysis.

Eight members in the three-generation pedigree complained about vision loss and seven of them had detailed clinical assessments, demonstrating ocular phenotypes including extramacular and vascular arcades subretinal deposits and Arden ratio decline on electrooculography that resembled ARB. Bilateral anterior chamber structure abnormalities were observed in seven cases and three patients were diagnosed with angle-closure glaucoma. Despite clinical phenotypes supporting ARB, there was only a single heterozygous mutation of c.227T > C (p.Ile76Thr) in the BEST1 gene detected in all eight patients, which showcased AD inheritance.

An ARB-like phenotype could be caused by a heterozygous mutation of the BEST1 gene and inherited in an AD fashion.