PURPOSE:: To describe the variable ocular phenotype associated with a heterozygous mutation in the BEST1 gene. METHODS:: Clinical and genetic assessment was performed in five members of the same family. Molecular genetic analysis of the BEST1 gene was performed by direct sequencing. Extensive ophthalmic examination included color fundus imaging, spectral domain optical coherence tomography, fundus autofluorescence, electro-oculography (EOG), and full-field electroretinography (ERG). The main outcome measures were BEST1 mutations, imaging, and electroretinography findings. RESULTS:: All affected family members carried a single heterozygous c.614T>C (p.I205T) mutation in exon 5 of the BEST1 gene. The 46-year-old proband showed nanophthalmos with chorioretinal atrophy in the macula, extensive coarse hyperpigmentation in the (mid) peripheral retina with tractional vitreous strands. Full-field ERG revealed nonrecordable cone and rod responses, and EOG showed an absent light rise. The daughter and son of the proband showed a phenotype resembling autosomal recessive bestrophinopathy, including short axial lengths, cystoid fluid collections, and shallow serous subretinal fluid accumulation on spectral domain optical coherence tomography throughout the macula in combination with mild retinal pigment epithelium changes. The son of the proband also showed subretinal yellowish deposits inferiorly in the macula as well as outside the temporal vascular arcade, that were hyperfluorescent on fundus autofluorescence, similar to those seen in autosomal recessive bestrophinopathy. Full-field ERG revealed a reduced rod and cone response and a markedly reduced or absent EOG light peak in both brother and sister of the proband. CONCLUSION:: The clinical spectrum of bestrophinopathy may encompass severe ocular phenotypes that affect the development and function of the entire eye. A clinical picture similar to autosomal recessive bestrophinopathy can also be caused by a single heterozygous mutation in the BEST1 gene, such as the c.614T>C (p.I205T) variant in this family.
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