Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Ophthalmology
Published in: BMC Ophthalmology 1/2023

Open Access 01-12-2023 | Night-Blindness | Case Report

Asymmetric presentation with a novel RP2 gene mutation in X-Linked retinitis pigmentosa: a case report

Authors: Hyun Woo Lee, Eun Kyoung Lee

Published in: BMC Ophthalmology | Issue 1/2023

Login to get access

Abstract

Background

We present the detailed multimodal imaging analysis in a case of X-linked retinitis pigmentosa (XLRP) exhibiting a markedly asymmetric presentation with a novel RP2 mutation.

Case presentation

A 25-year-old woman complained of decreased vision in the right eye as well as night blindness. Her visual acuity was 20/100 (OD) and 20/20 (OS). Fundus examination revealed bone spicule pigmentation with tessellated changes in the fundus within the posterior pole. Optical coherence tomography (OCT) showed generalized disruption of foveal microstructures in the OD. No abnormal findings were identified, but localized ellipsoid zone band losses were observed on OCT in the OS. Fundus autofluorescence revealed multiple patchy hypo-autofluorescent lesions in the OD and a tapetal-like radial reflex against a dark background in the OS. Fluorescein angiography and OCT angiography revealed diffuse mottled hyperfluorescence with reduced retinal vessel density in the OD and no evidence of vascular compromise in the OS. Goldmann perimetry demonstrated a constricted visual field, and electrophysiological assessment revealed an extinguished rod response and a severely impaired cone response in the OD. Molecular genetic tests via next-generation sequencing revealed the pathogenic variant to be a heterozygous frameshift mutation in RP2 (RP2, p.Glu269Glyfs*7), resulting in premature termination of the protein.

Conclusions

Random X-inactivation may be attributed to interocular differences in the severity of XLRP in female carriers. A novel frameshift mutation in the RP2 gene and a comprehensive phenotypic evaluation in the current study may broaden the spectrum of the disease in XLRP carriers.
Appendix
Available only for authorised users
Literature
1.
Zhang Q. Retinitis Pigmentosa: Progress and Perspective. Asia Pac J Ophthalmol (Phila). 2016;5:265–71.CrossRefPubMed
2.
3.
4.
5.
Daiger SP, Sullivan LS, Bowne SJ. Genes and mutations causing retinitis pigmentosa. Clin Genet. 2013;84:132–41.CrossRefPubMed
6.
Webb TR, Parfitt DA, Gardner JC, et al. Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23). Hum Mol Genet. 2012;21:3647–54.CrossRefPubMedPubMedCentral
7.
Shu X, Black GC, Rice JM, et al. RPGR mutation analysis and disease: an update. Hum Mutat. 2007;28:322–8.CrossRefPubMed
8.
Pelletier V, Jambou M, Delphin N, et al. Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype-phenotype correlations and impact on genetic counseling. Hum Mutat. 2007;28:81–91.CrossRefPubMed
9.
Breuer DK, Yashar BM, Filippova E, et al. A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa. Am J Hum Genet. 2002;70:1545–54.CrossRefPubMedPubMedCentral
10.
11.
Wu AL, Wang JP, Tseng YJ, et al. Multimodal Imaging of Mosaic Retinopathy in Carriers of Hereditary X-Linked Recessive Diseases. Retina. 2018;38:1047–57.CrossRefPubMed
12.
Wu H, Luo J, Yu H, et al. Cellular resolution maps of X chromosome inactivation: implications for neural development, function, and disease. Neuron. 2014;81:103–19.CrossRefPubMedPubMedCentral
13.
Evans RJ, Hardcastle AJ, Cheetham ME. Focus on molecules: X-linked Retinitis Pigmentosa 2 protein, RP2. Exp Eye Res. 2006;82:543–4.CrossRefPubMed
14.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.CrossRefPubMedPubMedCentral
15.
Jacobson SG, Yagasaki K, Feuer WJ, et al. Interocular asymmetry of visual function in heterozygotes of X-linked retinitis pigmentosa. Exp Eye Res. 1989;48:679–91.CrossRefPubMed
16.
Comander J, Weigel-DiFranco C, Sandberg MA, et al. Visual Function in Carriers of X-Linked Retinitis Pigmentosa. Ophthalmology. 2015;122:1899–906.CrossRefPubMed
17.
Sharon D, Sandberg MA, Rabe VW, et al. RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. Am J Hum Genet. 2003;73:1131–46.CrossRefPubMedPubMedCentral
18.
Jayasundera T, Branham KE, Othman M, et al. RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa. Arch Ophthalmol. 2010;128:915–23.CrossRefPubMedPubMedCentral
19.
Genead MA, Fishman GA, Lindeman M. Structural and functional characteristics in carriers of X-linked retinitis pigmentosa with a tapetal-like reflex. Retina. 2010;30:1726–33.CrossRefPubMedPubMedCentral
20.
Acton JH, Greenberg JP, Greenstein VC, et al. Evaluation of multimodal imaging in carriers of X-linked retinitis pigmentosa. Exp Eye Res. 2013;113:41–8.CrossRefPubMedPubMedCentral
21.
Ma K. Embryonic left-right separation mechanism allows confinement of mutation-induced phenotypes to one lateral body half of bilaterians. Am J Med Genet A. 2013;161A:3095–114.CrossRefPubMed
22.
Fujinami K, Liu X, Ueno S, et al. RP2-associated retinal disorder in a Japanese cohort: Report of novel variants and a literature review, identifying a genotype-phenotype association. Am J Med Genet C Semin Med Genet. 2020;184:675–93.CrossRefPubMed
23.
Miano MG, Testa F, Filippini F, et al. Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains. Hum Mutat. 2001;18:109–19.CrossRefPubMed
24.
De Silva SR, Arno G, Robson AG, et al. The X-linked retinopathies: Physiological insights, pathogenic mechanisms, phenotypic features and novel therapies. Prog Retin Eye Res. 2021;82: 100898.CrossRefPubMed
25.
26.
Schwahn U, Lenzner S, Dong J, et al. Positional cloning of the gene for X-linked retinitis pigmentosa 2. Nat Genet. 1998;19:327–32.CrossRefPubMed
27.
Mears AJ, Gieser L, Yan D, et al. Protein-truncation mutations in the RP2 gene in a North American cohort of families with X-linked retinitis pigmentosa. Am J Hum Genet. 1999;64:897–900.CrossRefPubMedPubMedCentral
28.
Hardcastle AJ, Thiselton DL, Van Maldergem L, et al. Mutations in the RP2 gene cause disease in 10% of families with familial X-linked retinitis pigmentosa assessed in this study. Am J Hum Genet. 1999;64:1210–5.CrossRefPubMedPubMedCentral
29.
Rosenberg T, Schwahn U, Feil S, et al. Genotype-phenotype correlation in X-linked retinitis pigmentosa 2 (RP2). Ophthalmic Genet. 1999;20:161–72.CrossRefPubMed
30.
Thiselton DL, Zito I, Plant C, et al. Novel frameshift mutations in the RP2 gene and polymorphic variants. Hum Mutat. 2000;15:580.CrossRefPubMed
31.
Wada Y, Nakazawa M, Abe T, et al. A new Leu253Arg mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2000;41:290–3.PubMed
32.
Schwahn U, Paland N, Techritz S, et al. Mutations in the X-linked RP2 gene cause intracellular misrouting and loss of the protein. Hum Mol Genet. 2001;10:1177–83.CrossRefPubMed
33.
Thomas PJ, Qu BH, Pedersen PL. Defective protein folding as a basis of human disease. Trends Biochem Sci. 1995;20:456–9.CrossRefPubMed
34.
Horner F, Wawrzynski J, MacLaren RE. Novel non-sense mutation in RP2 (c.843_844insT/p.Arg282fs) is associated with a severe phenotype of retinitis pigmentosa without evidence of primary retinal pigment epithelium involvement. BMJ Case Rep. 2019;12.
Metadata
Title
Asymmetric presentation with a novel RP2 gene mutation in X-Linked retinitis pigmentosa: a case report
Authors
Hyun Woo Lee
Eun Kyoung Lee
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2023
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-023-02968-4

Other articles of this Issue 1/2023

BMC Ophthalmology 1/2023 Go to the issue

Research

Donor lamella thickness after ultrathin Descemet stripping automated endothelial keratoplasty and its relation to postoperative visual acuity and pre-operative lamella measures

Case Report

A case of mitomycin C toxicity after XEN gel stent implantation with the XEN air technique in a glaucoma patient

Case report

Variants of BEST1 and CRYBB2 cause a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy: case report

Research article

Cataract surgery in neovascular AMD: impact on visual acuity and disease activity

Research

Ahmed to Baerveldt glaucoma drainage device exchange in pediatric patients

Case report

Long-term course with iris changes after trabeculectomy for uveitic glaucoma associated with iris mammillation: a case report