Clinical Characteristics of Twelve Patients in Nine Families With Autosomal Recessive Bestrophinopathy

Abstract

Purpose: : To report the clinical characteristics of patients with a recently described ocular disorder consequent upon biallelic mutation of the BEST1 gene.

Methods: : Twelve affected patients and 12 heterozygotes from nine families attending the retinal clinics at Moorfields Eye Hospital and Ghent University Hospital were examined, and underwent imaging (including autofluorescence and OCT) and electrophysiology incorporating ISCEV standard ERGs, PERG, and EOG. DNA was extracted and the BEST1 coding region and intron-exon boundaries sequenced.

Results: : All 6 female and 6 male patients had reduced visual acuity, were hyperopic and had irregularity of the RPE reflex with widespread subretinal deposits at presentation which first occurred at a median age of 20 years (range 4-40 years). Intra-retinal or subretinal fluid was present in one or both eyes of all patients. Four patients required treatment for angle-closure glaucoma. Autofluorescence imaging was particularly useful in diagnosis and showed a distinct irregular reflex throughout the posterior fundus in all patients. All cases had abnormality of both rod and cone full-field ERG responses, with delay in the cone flicker ERG. All had markedly subnormal or absent EOG light-rise, disproportionate to the degree of rod ERG abnormality, which directed mutational screening. None of the 12 examined heterozygotes had symptoms or signs of retinal disease, nor, in 11 heterozygotes, abnormalities of ERG or EOG. Progression in ERG abnormality was documented in three families. Of 18 potential disease causing alleles, mutations were found in 16, including 2 nonsense alleles.

Conclusions: : Biallelic mutation of BEST1 causes autosomal recessive bestrophinopathy which has a fundus and functional phenotype unlike that of Best disease. Heterozygotes do not manifest subclinical retinal dysfunction.

Keywords: retinal degenerations: hereditary • genetics • electroretinography: clinical