TY - JOUR
T1 - RP2-associated retinal disorder in a Japanese cohort
T2 - Report of novel variants and a literature review, identifying a genotype–phenotype association
AU - Fujinami, Kaoru
AU - Liu, Xiao
AU - Ueno, Shinji
AU - Mizota, Atsushi
AU - Shinoda, Kei
AU - Kuniyoshi, Kazuki
AU - Fujinami-Yokokawa, Yu
AU - Yang, Lizhu
AU - Arno, Gavin
AU - Pontikos, Nikolas
AU - Kameya, Shuhei
AU - Kominami, Taro
AU - Terasaki, Hiroko
AU - Sakuramoto, Hiroyuki
AU - Nakamura, Natsuko
AU - Kurihara, Toshihide
AU - Tsubota, Kazuo
AU - Miyake, Yozo
AU - Yoshiake, Kazutoshi
AU - Iwata, Takeshi
AU - Tsunoda, Kazushige
N1 - Funding Information:
Gavin Arno is supported by a Fight for Sight (UK) Early Career Investigator Award, NIHR-BRC at Moorfields Eye Hospital and the UCL Institute of Ophthalmology, NIHR-BRC at Great Ormond Street Hospital and UCL Institute of Child Health, and Great Britain Sasakawa Foundation Butterfield Award, UK. Nikolas Pontikos is funded by a Moorfields Eye Charity Career Development Award (R190031A), the NIHR-BRC at Moorfields Eye Hospital and the UCL Institute of Ophthalmology. Toshihide Kurihara is supported by Tsubota Laboratory, Inc., Fuji Xerox Co., Ltd., Kirin Company, Ltd., Kowa Company, Ltd., Novartis Pharmaceuticals, Santen Pharmaceutical Co. Ltd., and ROHTO Pharmaceutical Co., Ltd. Takeshi Iwata is supported by Japan Agency for Medical Research and Development (AMED) (18ek0109282h0002). Kazushige Tsunoda is supported by AMED, the Ministry of Health, Labor and Welfare, Japan (18ek0109282h0002), Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Japan (H26-26462674), grants from National Hospital Organization Network Research Fund, Japan (H30-NHO-Sensory Organs-03), and Novartis Research Grant (2018). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - The retinitis pigmentosa 2 (RP2) gene is one of the causative genes for X-linked inherited retinal disorder. We characterized the clinical/genetic features of four patients with RP2-associated retinal disorder (RP2-RD) from four Japanese families in a nationwide cohort. A systematic review of RP2-RD in the Japanese population was also performed. All four patients were clinically diagnosed with retinitis pigmentosa (RP). The mean age at examination was 36.5 (10–47) years, and the mean visual acuity in the right/left eye was 1.40 (0.52–2.0)/1.10 (0.52–1.7) in the logarithm of the minimum angle of resolution unit, respectively. Three patients showed extensive retinal atrophy with macular involvement, and one had central retinal atrophy. Four RP2 variants were identified, including two novel missense (p.Ser6Phe, p.Leu189Pro) and two previously reported truncating variants (p.Arg120Ter, p.Glu269CysfsTer3). The phenotypes of two patients with truncating variants were more severe than the phenotypes of two patients with missense variants. A systematic review revealed additional 11 variants, including three missense and eight deleterious (null) variants, and a statistically significant association between phenotype severity and genotype severity was revealed. The clinical and genetic spectrum of RP2-RD was illustrated in the Japanese population, identifying the characteristic features of a severe form of RP with early macular involvement.
AB - The retinitis pigmentosa 2 (RP2) gene is one of the causative genes for X-linked inherited retinal disorder. We characterized the clinical/genetic features of four patients with RP2-associated retinal disorder (RP2-RD) from four Japanese families in a nationwide cohort. A systematic review of RP2-RD in the Japanese population was also performed. All four patients were clinically diagnosed with retinitis pigmentosa (RP). The mean age at examination was 36.5 (10–47) years, and the mean visual acuity in the right/left eye was 1.40 (0.52–2.0)/1.10 (0.52–1.7) in the logarithm of the minimum angle of resolution unit, respectively. Three patients showed extensive retinal atrophy with macular involvement, and one had central retinal atrophy. Four RP2 variants were identified, including two novel missense (p.Ser6Phe, p.Leu189Pro) and two previously reported truncating variants (p.Arg120Ter, p.Glu269CysfsTer3). The phenotypes of two patients with truncating variants were more severe than the phenotypes of two patients with missense variants. A systematic review revealed additional 11 variants, including three missense and eight deleterious (null) variants, and a statistically significant association between phenotype severity and genotype severity was revealed. The clinical and genetic spectrum of RP2-RD was illustrated in the Japanese population, identifying the characteristic features of a severe form of RP with early macular involvement.
KW - RP2 gene
KW - X-linked recessive
KW - inherited retinal disorder
KW - retinitis pigmentosa
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U2 - 10.1002/ajmg.c.31830
DO - 10.1002/ajmg.c.31830
M3 - Article
C2 - 32875684
AN - SCOPUS:85090067044
VL - 184
SP - 675
EP - 693
JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
SN - 1552-4868
IS - 3
ER -