Nonsense-Mediated Decay as the Molecular Cause for Autosomal Recessive Bestrophinopathy in Two Unrelated Families

Abstract

In truncating BEST1 mutations, the null phenotype associated with ARB is attributed to a substantial decrease of BEST1 expression promoted by the nonsense-mediated decay (NMD) surveillance mechanism. Moreover, the severity of the phenotype increases with the preserved amount of altered transcript, suggesting that the clinical outcome reflects the combined null and dominant negative effects of the two mutations over the patient's genetic background.