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Cone dysfunction in ARR3-mutation-associated early-onset high myopia: an electrophysiological study.

Tamás Fehér1, Noémi Széll2, István Nagy3,4

  • 1Institute of Biochemistry, HUN-REN Biological Research Centre, 62 Temesvari krt., Szeged, H6726, Hungary. fehert@brc.hu.

Orphanet Journal of Rare Diseases
|October 18, 2024
PubMed
Summary

Myopia-26, caused by ARR3 gene mutations, leads to cone dysfunction in affected females, independent of eye elongation. This suggests a specific role for ARR3 in myopia development.

Keywords:
ARR3Cone arrestinCone dysfunctionEarly onset high myopiaElectroretinogramRetina

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Area of Science:

  • Ophthalmology
  • Genetics
  • Retinal Physiology

Background:

  • Myopia-26 is a rare Mendelian form of early-onset high-myopia (eoHM) linked to mutations in the X-chromosomal ARR3 gene.
  • This condition predominantly affects females and offers a unique model to study retinal mechanisms in pathological eye growth.

Purpose of the Study:

  • To investigate the electrophysiological characteristics of Myopia-26 patients.
  • To differentiate the effects of ARR3 mutations from general high myopia on retinal function.

Main Methods:

  • A case-control study involving 26 participants: healthy controls, high myopes without ARR3 mutations, and Myopia-26 patients.
  • Full-field electroretinograms (ERGs) were recorded under light and dark-adapted conditions.
  • Genetic analysis confirmed ARR3 gene status.

Main Results:

  • Myopia-26 patients exhibited significantly reduced best-corrected visual acuity (BCVA) compared to controls.
  • Light-adapted ERG amplitudes (a- and b-waves) were reduced by ~35% in Myopia-26 patients and ~55% in ARR3 mutation carriers.
  • Dark-adapted a-wave amplitudes showed a ~20% reduction in all myopic patients, regardless of ARR3 genotype.

Conclusions:

  • Cone dysfunction in Myopia-26 patients is directly attributable to ARR3 mutations, not solely to eye elongation.
  • The ARR3 mutation may contribute to myopic refractive error development via an as-yet-unconfirmed pathway.