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. 2019 Mar 26;20(6):1518.
doi: 10.3390/ijms20061518.

X-linked Retinitis Pigmentosa in Japan: Clinical and Genetic Findings in Male Patients and Female Carriers

Kentaro Kurata  1 , Katsuhiro Hosono  2 , Takaaki Hayashi  3 , Kei Mizobuchi  4 , Satoshi Katagiri  5 , Daisuke Miyamichi  6 , Sachiko Nishina  7 , Miho Sato  8 , Noriyuki Azuma  9 , Tadashi Nakano  10 , Yoshihiro Hotta  11
Affiliations

X-linked Retinitis Pigmentosa in Japan: Clinical and Genetic Findings in Male Patients and Female Carriers

Kentaro Kurata et al. Int J Mol Sci. .

Abstract

X-linked retinitis pigmentosa (XLRP) is a type of severe retinal dystrophy, and female carriers of XLRP demonstrate markedly variable clinical severity. In this study, we aimed to elucidate the clinical findings of male patients with and female carriers of XLRP in a Japanese cohort and demonstrate the genetic contribution. Twelve unrelated families (13 male patients, 15 female carriers) harboring pathogenic mutations in RPGR or RP2 were included, and comprehensive ophthalmic examinations were performed. To identify potential pathogenic mutations, targeted next-generation sequencing was employed. Consequently, we identified 11 pathogenic mutations, of which five were novel. Six and five mutations were detected in RPGR and RP2, respectively. Only one mutation was detected in ORF15. Affected male patients with RP2 mutations tended to have lower visual function than those with RPGR mutations. Female carriers demonstrated varying visual acuities and visual fields. Among the female carriers, 92% had electroretinographical abnormalities and 63% had a radial autofluorescent pattern, and the carriers who had higher myopia showed worse visual acuity and more severe retinal degeneration. Our results expand the knowledge of the clinical phenotypes of male patients with and female carriers of XLRP and suggest the possibility that RP2 mutations are relatively highly prevalent in Japan.

Keywords: RP2; RPGR; X-linked inheritance; genetic findings; retinitis pigmentosa; visual function.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The pedigrees of the families in this study. Closed and open symbols represent affected and unaffected individuals, respectively. Dotted circles represent female carriers. Arrows indicate probands. The slash indicates a deceased person. M refers to the mutant allele and + to the normal allele.
Figure 2
Figure 2
Correlation between visual function and age among affected male subjects in this study. The graphs show visual acuity values expressed in logMAR units (a), refractive error (b), visual field extent with the V-4e isopter (c), and visual field extent with the I-4e isopter (d) versus age. The data from the same subject are indicated using bars connecting the points.
Figure 3
Figure 3
Correlation between visual function and age among carrier female subjects in this study. The graphs show visual acuity values expressed in logMAR units (a), refractive error (b), visual field extent with the V-4e isopter (c), and visual field extent with the I-4e isopter (d) versus age. The data from the same subject are indicated using bars connecting the points.
Figure 4
Figure 4
Color fundus photography, fundus autofluorescence (FAF), and optic coherence tomography (OCT) of carrier female subjects in this study. (a) Fundus findings of Carrier 15. Color fundus photography revealed no abnormalities (grade 0). FAF revealed a somewhat radial pattern. No obvious abnormalities were detected on OCT. (b) Fundus findings of Carrier 2. Tapetal reflex was detected temporal to the macula (grade 1). FAF revealed a radial pattern and there were no obvious abnormalities on OCT. (c) Fundus findings of Carrier 13. Pigmentary change was detected in the temporal peripheral retina (grade 2). FAF showed a radial autofluorescent pattern. The ellipsoid zone was extinguished in the temporal retina on OCT. (d) Fundus findings of Carrier 1. Diffuse retinal atrophy including pigmentary disturbance was observed (grade 3). FAF showed a radial autofluorescent pattern and hypoautofluorescence consistent with retinal pigment epithelium atrophy. OCT showed severe atrophy of the outer retina and choroid. Scar bar = 200 µm.
Figure 5
Figure 5
Correlation between visual function and age among affected male subjects with RPGR or RP2 mutation. Black dots and lines indicate the data of affected male subjects with RPGR mutation and gray dots and lines indicate the data of affected male subjects with RP2 mutation. The graphs show visual acuity values expressed in logMAR units (a), refractive error (b), visual field extent with the V-4e isopter (c), and visual field extent with the I-4e isopter (d) versus age. The data from the same subject are indicated using bars connecting the points.
Figure 6
Figure 6
Correlation between refractive error and visual function among carrier female subjects. The graphs show visual acuity values expressed in logMAR units (a), visual field extent with the V-4e isopter (b), and visual field extent with the I-4e isopter (c) versus refractive error. The data from the same subject are indicated using bars connecting the points.
Figure 7
Figure 7
Association of the severity between affected male and carrier female subjects. The data from the same subject are indicated using bars connecting the points. (a) Black and gray diamonds indicate the severe and mild phenotypic groups, respectively. Affected male subjects were divided into two groups according to their phenotypic severity. Visual acuity above the regression line was defined as mild (mild group). Conversely, visual acuity below the regression line was defined as severe (severe group). (b) The data of carrier female subjects whose intrafamilial affected male subjects were classified into the severe group are indicated with black diamonds. Conversely, the data of carrier female subjects whose intrafamilial affected male subjects were classified into the mild group are indicated by gray diamonds.
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