Biallelic Mutations in the BEST1 Gene: Additional Families with Autosomal Recessive Bestrophinopathy

To describe the genotype and phenotype of patients with autosomal recessive bestrophinopathy (ARB), and heterozygous carriers.

The members of three unrelated ARB families were investigated. Molecular genetic analysis was performed on 11 members of these families. Ten members were examined clinically; including visual acuity, slit-lamp examination, biomicroscopy, fundus photography, and Goldmann applanation tonometry. Measurements were also made of the anterior chamber depth and axial length, and optical coherence tomography (OCT), electrooculography (EOG), and full-field electroretinography (full-field ERG) were performed. Multifocal electroretinography (mfERG) was performed on eight members of these families.

Two novel combinations of missense mutations in the BEST1 gene were identified: p.R141H/p.M325T in three patients with ARB in two unrelated Norwegian families, and p.R141H/p.I201T was found in an ARB patient in a Swedish family. All four patients with ARB had clinical and electrophysiological features of ARB. All the heterozygous carriers of the p.R141H mutation were clinically normal, and showed normal OCT, EOG and full-field ERG findings, but had mildly abnormal mfERG results. Only one heterozygous carrier of the p.M325T mutation was studied and he was clinically normal, showing normal OCT and full-field ERG results, but subnormal EOG and mfERG findings. The heterozygous carrier of the p.I201T mutation was clinically normal, showing normal OCT, EOG and full-field ERG results, but subnormal mfERG results.

We have shown that the two novel combinations of compound heterozygous mutations p.R141H/p.M325T and p.R141H/p.I201T in the BEST1 gene can also lead to the ARB phenotype.