ARR4 has been associated with X-linked, female-limited, high
myopia. However, using exome sequencing (ES) in a Southern Chinese
family, we identified the first hemizygous high myopia case in a male
patient. A novel truncated mutation (ARR4: c.569C>G,
p.S190*), which co-segregated with the disease phenotype in affected
members, was identified in this family. Because the proband’s father was
a hemizygote for the ARR4 variant, the present study demonstrated
a case where high myopia caused by ARR4 is not X-linked,
female-limited. This implied that a complicated X-linked inheritance
pattern may exist for ARR4. Thus, the results of this study
expanded the variant spectrum in ARR4 and provided additional
information for genetic counseling, prenatal testing and diagnosis.
Moreover, we characterized the pathogenic role of ARR4
c.569C>G (p.S190*) and demonstrated that the mutant protein
accumulated under ER stress and was degraded by the proteasome.