Mutationsabhängige Mechanismen und deren Bedeutung für zielgerichtete Behandlungsstrategien am Beispiel von Bestrophin 1 und den Bestrophinopathien

Bestrophin 1 (BEST1) encodes an integral membrane protein localized in the basolateral aspect of the retinal pigment epithelium. Mutations in BEST1 are associated with distinct retinal dystrophies, the so-called "bestrophinopathies", often causing visual impairment, even in early childhood. The clinical entities of the bestrophinopathies can be distinguished by phenotypic characteristics and mode of inheritance of the respective gene defect. While the autosomal dominant inheritance pattern with one altered copy of BEST1 is common, heterozygous carriers of the autosomal recessive bestrophinopathy are generally but not consistently symptom-free. This review highlights the significance of understanding the underlying molecular mechanisms that contribute to disease pathogenesis of autosomal dominant and autosomal recessive bestrophinopathies. This knowledge is deemed crucial and needs to be considered in future planning of treatment strategies.