Clinical characteristics of high myopia in female carriers of pathogenic RPGR mutations: a case series and review of the literature

ABSTRACT

Background

RPGR mutations are the most common cause of X-linked retinitis pigmentosa (XLRP). High myopia has been described as a very frequent feature among affected female carriers of XLRP. However, the clinical phenotype of female patients presenting with X-linked RPGR-related high myopia has not been well described.

Materials and Methods

Retrospective case series of four female patients with RPGR mutations and a diagnosis of high myopia, who presented to two academic eye centers. Clinical data, including age, family history, visual acuity, refractive error, dilated fundus exam, fundus photography, optical coherence tomography, electroretinography, and results of genetic testing, were collected.

Results

Three RPGR variants identified in the present study have not been previously associated with myopia in female carriers. One variant (c.2405_2406delAG, p.Glu802Glyfs *32) has been previously associated with a myopic phenotype in a female patient. Patients became symptomatic between the first and sixth decades of life. Myopia-associated tilted optic discs and posterior staphyloma were present in all patients. Two patients presented with intraretinal migration of the retinal pigment epithelium.

Conclusion

RPGR-related high myopia has been associated with mutations in exons 1–14 and ORF15 in heterozygous females. There is a wide range of visual function among carriers. Although the exact mechanism of RPGR-related high myopia is still unclear, continued molecular diagnosis and description of phenotypes remain a crucial step in understanding the impact of RPGR mutations on visual function in female XLRP carriers.

KEYWORDS:

• Retinitis pigmentosa
• x-linked retinitis pigmentosa
• XLRP
• retinitis pigmentosa GTPase regulator
• RPGR
• female carriers
• myopia

Acknowledgements

The authors give thanks to Dr. Michael W. Gaynon for manuscript review.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Institutional review board statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of all participating institutions.

Informed consent statement

Informed consent was obtained from all subjects involved in the study.

Additional information

Funding

This work was supported by NIH/NEI K08-EY022058 (Y.S.), R01-EY025295 (Y.S.), VA merit CX001298 (Y.S.), Children’s Health Research Institute Award (Y.S.). Research for Prevention of Blindness Unrestricted grant (Stanford Ophthalmology), P30 Vision Center grant to Stanford Ophthalmology department. Y.S. is a Laurie Kraus Lacob Faculty Scholar in Pediatric Translational Medicine. S.H.T is supported by 5P30CA013696, U01EY030580, U54OD020351, R24EY028758, R24EY027285, 5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437, the Schneeweiss Stem Cell Fund, New York State, the Foundation Fighting Blindness (FFB) New York Regional Research Center Grant, FFB Translational Research Acceleration Program (TRAP) Award, Nancy & Kobi Karp, the Crowley Family Funds, The Rosenbaum Family Foundation, Alcon Research Institute, the Gebroe Family Foundation, the Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, New York, NY, USA. S.H.T. has received support from Abeona Therapeutics, Inc. and Emendo. S.H.T. is the founder of Rejuvitas. T.K. is supported by NIH/NEI F32-EY032775-01 Kirschstein-NRSA postdoctoral fellowship. The authors declare no financial competing interests