A novel missense mutation in BEST1 associated with an autosomal-dominant vitreoretinochoroidopathy (ADVIRC) phenotype

To report a 68-year-old female with an autosomal-dominant vitreoretinochoroidopathy (ADVIRC) phenotype associated with a subretinal hemorrhage (SRH) and novel BEST1 pathogenic variation p.Met571Thr.

The patient was assessed by fundus photography, fluorescence and indocyanine green angiography, spectral-domain optical coherence tomography, photopic and scotopic electroretinogram (ERG), and electrooculogram (EOG). Whole-exome and Sanger sequencing of the patient's and selected family members' DNA was performed. Ophthalmoscopic examinations were also performed on six patient's relatives.

The patient presented moderate vitreous and SRH in the left eye. A distinct, annular hyperpigmented band was present in both eyes. Vitrectomy improved visual acuity, and the SRH gradually regressed without recurrence. Preserved macular function was shown by optical coherence tomography (OCT). Genetic analysis identified a novel heterozygous mutation, resulting in p.Met571Thr in BEST1. No mutations were observed in a panel of other eye disease genes, suggesting that this pathogenic variation in BEST1 is associated with an ADVIRC phenotype. No other evaluated family member had the variant or the fundus findings.

We present a patient with a novel p.Met571Thr pathogenic variation associated with an ADVIRC phenotype. SRH is a unique finding in ADVIRC patients and may correspond to peripheral exudative hemorrhagic chorioretinopathy. The BEST1 pathogenic variation p.Met571Thr might be the likely cause of ADVIRC in this patient. However, further study is necessary to determine whether this mutation is causative.