Identification and Functional Characterization of a Novel Nonsense Variant in ARR3 in a Southern Chinese Family With High Myopia

Abstract

<i>ARR3</i> has been associated with X-linked, female-limited, high myopia. However, using exome sequencing (ES), we identified the first high myopia case with hemizygous <i>ARR3</i>-related mutation in a male patient in a Southern Chinese family. This novel truncated mutation (<i>ARR3</i>: c.569C>G, p.S190*) co-segregated with the disease phenotype in affected family members and demonstrated that high myopia caused by <i>ARR3</i> is not X-linked, female-limited, where a complicated X-linked inheritance pattern may exist. Thus, our case expanded the variant spectrum in <i>ARR3</i> and provided additional information for genetic counseling, prenatal testing, and diagnosis. Moreover, we characterized the nonsense-mediated decay of the <i>ARR3</i> mutant mRNA and discussed the possible underlying pathogenic mechanisms.