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 phosphorated-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 in female carriers, and protan/deutan color vision defect affecting both genders. Using ten years of clinical follow-up data, we identified gradually worsen cone dysfunction/color vision as a key feature among affected individuals. We present a hypothesis of unbalanced color-vision signal output that had lowered blue color contribution from cone cells could potentially explain the etiology of this disease.