Identification and Functional Characterization of a Novel Nonsense Variant in ARR3 in a Southern Chinese Family With High Myopia
Dejian Yuan, Tizhen Yan, Shiqiang Luo, Jun Huang, Jianqiang Tan, Jianping Zhang, Victor Wei Zhang, Yueyuan Lan, Taobo Hu, Jing Guo, Mingwei Huang, Dingyuan Zeng
Abstract
ARR3 has been associated with X-linked, female-limited, high myopia. However, using exome sequencing (ES), we identified the first high myopia case with hemizygous ARR3 -related mutation in a male patient in a Southern Chinese family. This novel truncated mutation ( ARR3 : c.569C>G, p.S190*) co-segregated with the disease phenotype in affected family members and demonstrated that high myopia caused by ARR3 is not X-linked, female-limited, where a complicated X-linked inheritance pattern may exist. Thus, our case expanded the variant spectrum in ARR3 and provided additional information for genetic counseling, prenatal testing, and diagnosis. Moreover, we characterized the nonsense-mediated decay of the ARR3 mutant mRNA and discussed the possible underlying pathogenic mechanisms.