A Chinese Family with X-Linked Female-Limited High Myopia Caused by an ARR3 Variant

作者：J. Zhang, Yijia Zhao, Yueyuan Lan, Wenhui Liu, Pei Zhong, Binbin Wang · 发表于：Genetic Testing and Molecular Biomarkers · 年份：2026 · DOI：10.1177/19450265261419296 · 研究领域：Ophthalmology and Visual Impairment Studies、Connexins and lens biology、Glaucoma and retinal disorders

Background: X-linked female-limited high myopia (MYP26, OMIM:301010) is a rare Mendelian subtype of early-onset high myopia (eoHM), with females having progressive myopic refractive error (≥−6 D) and males as asymptomatic carriers. Pathogenic variants in ARR3 (OMIM:301770) have been linked to eoHM, but the spectrum of ARR3 variants in Chinese populations remains incompletely defined. Objective: To identify the causative variant in a Chinese eoHM family and expand ARR3 variant spectrum for MYP26. Methods: We conducted clinical and genetic analyses of a Chinese family with eoHM. The proband underwent clinical examinations and whole-exome sequencing (WES). Sanger sequencing validated variants in affected family members, and bioinformatics tools evaluated variant pathogenicity. Results: WES identified an ARR3 c.214C>T (p.R72X) stop-gain variant, co-segregating with the disease phenotype and predicted to truncate cone arrestin, disrupting phototransduction. A female carrier showing incomplete penetrance (I-1) was identified, which highlights the unrecognized complexity of the pathogenic mechanism underlying MYP26. This variant was first reported in the Chinese population. Conclusions: Our study expands the ARR3 variant spectrum associated with eoHM, highlighting the role of ARR3 c.214C>T (p.R72X), first reported in Chinese populations. The finding of incomplete penetrance underscores the complexity of X-linked female-limited inheritance and provides a reference for genetic c...