The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene

Mays Talib, Mary J van Schooneveld, Caroline Van Cauwenbergh, Jan Wijnholds, Jacoline B Ten Brink, Ralph J Florijn, Nicoline E Schalij-Delfos, Gislin Dagnelie, Maria M van Genderen, Elfride De Baere, Magda A Meester-Smoor, Julie De Zaeytijd, Frans P M Cremers, L Ingeborgh van den Born, Alberta A Thiadens, Carel B Hoyng, Caroline C Klaver, Bart P Leroy, Arthur A Bergen, Camiel J F Boon

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Purpose: The purpose of this study was to investigate the phenotype and long-term clinical course of female carriers of RPGR mutations.

Methods: This was a retrospective cohort study of 125 heterozygous RPGR mutation carriers from 49 families.

Results: Eighty-three heterozygotes were from retinitis pigmentosa (RP) pedigrees, 37 were from cone-/cone-rod dystrophy (COD/CORD) pedigrees, and 5 heterozygotes were from pedigrees with mixed RP/CORD or unknown diagnosis. Mutations were located in exon 1-14 and in ORF15 in 42 of 125 (34%) and 83 of 125 (66%) subjects, respectively. The mean age at the first examination was 34.4 years (range, 2.1 to 86.0 years). The median follow-up time in heterozygotes with longitudinal data (n = 62) was 12.2 years (range, 1.1 to 52.2 years). Retinal pigmentary changes were present in 73 (58%) individuals. Visual symptoms were reported in 51 (40%) cases. Subjects with both symptoms and pigmentary fundus changes were older than the other heterozygotes (P = 0.01) and had thinner foveal outer retinas (P = 0.006). Complete expression of the RP or CORD phenotype was observed in 29 (23%) heterozygotes, although usually in milder forms than in affected male relatives. Best-corrected visual acuity (BCVA) was <20/40 and <20/400 in at least one eye in 45 of 116 (39%) and 11 of 116 (9%) heterozygotes, respectively. Myopia was observed in 74 of 101 (73%) subjects and was associated with lower BCVA (P = 0.006). Increasing age was associated with lower BCVA (P = 0.002) and decreasing visual field size (P = 0.012; I4e isopter).

Conclusions: RPGR mutations lead to a phenotypic spectrum in female carriers, with myopia as a significantly aggravating factor. Complete disease expression is observed in some individuals, who may benefit from future (gene) therapeutic options.

Original languageEnglish
Pages (from-to)4123-4133
Number of pages11
JournalInvestigative ophthalmology & visual science
Volume59
Issue number10
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Eye Proteins/genetics
  • Female
  • Heterozygote
  • Humans
  • Middle Aged
  • Myopia/complications
  • Phenotype
  • Retinal Pigment Epithelium/pathology
  • Retinitis Pigmentosa/genetics
  • Retrospective Studies
  • Visual Acuity/physiology
  • Young Adult

Fingerprint Dive into the research topics of 'The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene'. Together they form a unique fingerprint.

  • Cite this

    Talib, M., van Schooneveld, M. J., Van Cauwenbergh, C., Wijnholds, J., Ten Brink, J. B., Florijn, R. J., Schalij-Delfos, N. E., Dagnelie, G., van Genderen, M. M., De Baere, E., Meester-Smoor, M. A., De Zaeytijd, J., Cremers, F. P. M., van den Born, L. I., Thiadens, A. A., Hoyng, C. B., Klaver, C. C., Leroy, B. P., Bergen, A. A., & Boon, C. J. F. (2018). The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene. Investigative ophthalmology & visual science, 59(10), 4123-4133. https://doi.org/10.1167/iovs.17-23453