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

Abstract

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 counseling of related families.