International Journal of Molecular Sciences (Jan 2020)

<i>RPGR</i>-Associated Dystrophies: Clinical, Genetic, and Histopathological Features

  • Xuan-Thanh-An Nguyen,
  • Mays Talib,
  • Mary J. van Schooneveld,
  • Joost Brinks,
  • Jacoline ten Brink,
  • Ralph J. Florijn,
  • Jan Wijnholds,
  • Robert M. Verdijk,
  • Arthur A. Bergen,
  • Camiel J.F. Boon

DOI
https://doi.org/10.3390/ijms21030835
Journal volume & issue
Vol. 21, no. 3
p. 835

Abstract

Read online

This study describes the clinical, genetic, and histopathological features in patients with RPGR-associated retinal dystrophies. Nine male patients from eight unrelated families underwent a comprehensive ophthalmic examination. Additionally, the histopathology of the right eye from a patient with an end-stage cone-rod-dystrophy (CRD)/sector retinitis pigmentosa (RP) phenotype was examined. All RPGR mutations causing a CRD phenotype were situated in exon ORF15. The mean best-corrected visual acuity (BCVA, decimals) was 0.58 (standard deviation (SD)): 0.34; range: 0.05−1.13); and the mean spherical refractive error was −4.1 D (SD: 2.11; range: −1.38 to −8.19). Hyperautofluorescent rings were observed in six patients. Full-field electroretinography responses were absent in all patients. The visual field defects ranged from peripheral constriction to central islands. The mean macular sensitivity on microperimetry was 11.6 dB (SD: 7.8; range: 1.6−24.4) and correlated significantly with BCVA (r = 0.907; p = 0.001). A histological examination of the donor eye showed disruption of retinal topology and stratification, with a more severe loss found in the peripheral regions. Reactive gliosis was seen in the inner layers of all regions. Our study demonstrates the highly variable phenotype found in RPGR-associated retinal dystrophies. Therapies should be applied at the earliest signs of photoreceptor degeneration, prior to the remodeling of the inner retina.

Keywords