The causal mutation in ARR3 gene for high myopia and progressive color vision defect

Abstract

The ARR3 gene, also known as cone arrestin, belongs to the arrestin family and is expressed in cone cells, inactivating phosphorylated-opsins and preventing cone signals. Variants of ARR3 reportedly cause X-linked dominant female-limited early-onset (age < 7 years old) high myopia (< − 6D). Here, we reveal a new mutation (c.228T>A, p.Tyr76*) in ARR3 gene that can cause early-onset high myopia (eoHM) limited to female carriers. Protan/deutan color vision defects were also found in family members, affecting both genders. Using ten years of clinical follow-up data, we identified gradually worsening cone dysfunction/color vision as a key feature among affected individuals. We present a hypothesis that higher visual contrast due to the mosaic of mutated ARR3 expression in cones contributes to the development of myopia in female carriers.