Kaoru Fujinami1, Lizhu Yang2, Kwangsic Joo3, Kazushige Tsunoda4, Shuhei Kameya5, Gen Hanazono4, Yu Fujinami-Yokokawa6, Gavin Arno7, Mineo Kondo8, Natsuko Nakamura9, Toshihide Kurihara10, Kazuo Tsubota10, Xuan Zou11, Hui Li11, Kyu Hyung Park3, Takeshi Iwata12, Yozo Miyake13, Se Joon Woo14, Ruifang Sui15. 1. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; UCL Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom. Electronic address: k.fujinami@ucl.ac.uk. 2. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. 3. Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. 4. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. 5. Department of Ophthalmology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan. 6. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Graduate School of Health Management, Keio University, Tokyo, Japan. 7. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; UCL Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom. 8. Department of Ophthalmology, Graduate School of Medicine, Mie University, Mie, Japan. 9. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, The University of Tokyo, Tokyo, Japan. 10. Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. 11. Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. 12. Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. 13. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Aichi Medical University, Nagakute, Aichi, Japan. 14. Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. Electronic address: sejoon1@snu.ac.kr. 15. Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: hrfsui@163.com.
Abstract
PURPOSE: To describe the clinical and genetic characteristics of the cohort enrolled in the East Asian studies of occult macular dystrophy (OMD). DESIGN: International, multicenter, retrospective cohort studies. PARTICIPANTS: A total of 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e., Miyake disease) were enrolled from 3 centers in Japan, China, and South Korea. METHODS: A detailed history was obtained, and comprehensive ophthalmological examinations including spectral-domain OCT were performed. All detected sequence variants in the RP1L1 gene were reviewed, and in silico analysis was performed, including allele frequency analyses and pathogenicity predictions. MAIN OUTCOME MEASURES: Onset of disease, visual acuity (VA) converted to the logarithm of the minimum angle of resolution (logMAR), OCT findings, and effect of detected variants. RESULTS: Eleven families from Japan, 6 from South Korea, and 4 from China were recruited. There were 12 female and 24 male participants. The median age of onset was 25.5 years (range, 2-73), and the median age at the latest examination was 46.0 years (range, 11-86). The median VA (logMAR) was 0.65 (range, -0.08-1.22) in the right eye and 0.65 (-0.08-1.10) in the left eye. A significant correlation between onset of disease and VA was revealed. The Classical morphologic phenotype showing both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors was demonstrated in 30 patients (83.3%), and subtle photoreceptor architectural changes were demonstrated in 6 patients (16.6%). Eight pathogenic RP1L1 variants were identified, including 6 reported variants and 1 novel variant: p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent: p.R45W (11 families, 52.4%) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 10 families (47.6%) were located within the previously reported unique motif, including 6 amino acids (1196-1201). CONCLUSIONS: There is a large spectrum of clinical findings in Miyake disease, including various onset of disease and VA, whereas the characteristic photoreceptor microstructures were shared in most cases. Two hot spots including amino acid numbers 45 and 1196-1201 in the RP1L1 gene were confirmed in the East Asian population.
PURPOSE: To describe the clinical and genetic characteristics of the cohort enrolled in the East Asian studies of occult macular dystrophy (OMD). DESIGN: International, multicenter, retrospective cohort studies. PARTICIPANTS: A total of 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e., Miyake disease) were enrolled from 3 centers in Japan, China, and South Korea. METHODS: A detailed history was obtained, and comprehensive ophthalmological examinations including spectral-domain OCT were performed. All detected sequence variants in the RP1L1 gene were reviewed, and in silico analysis was performed, including allele frequency analyses and pathogenicity predictions. MAIN OUTCOME MEASURES: Onset of disease, visual acuity (VA) converted to the logarithm of the minimum angle of resolution (logMAR), OCT findings, and effect of detected variants. RESULTS: Eleven families from Japan, 6 from South Korea, and 4 from China were recruited. There were 12 female and 24 male participants. The median age of onset was 25.5 years (range, 2-73), and the median age at the latest examination was 46.0 years (range, 11-86). The median VA (logMAR) was 0.65 (range, -0.08-1.22) in the right eye and 0.65 (-0.08-1.10) in the left eye. A significant correlation between onset of disease and VA was revealed. The Classical morphologic phenotype showing both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors was demonstrated in 30 patients (83.3%), and subtle photoreceptor architectural changes were demonstrated in 6 patients (16.6%). Eight pathogenic RP1L1 variants were identified, including 6 reported variants and 1 novel variant: p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent: p.R45W (11 families, 52.4%) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 10 families (47.6%) were located within the previously reported unique motif, including 6 amino acids (1196-1201). CONCLUSIONS: There is a large spectrum of clinical findings in Miyake disease, including various onset of disease and VA, whereas the characteristic photoreceptor microstructures were shared in most cases. Two hot spots including amino acid numbers 45 and 1196-1201 in the RP1L1 gene were confirmed in the East Asian population.
Authors: Olga Zabek; Ioannis Lamprakis; Annekatrin Rickmann; Giacomo Calzetti; Bence György; Hendrik P N Scholl; Maria Della Volpe Waizel Journal: Am J Ophthalmol Case Rep Date: 2022-04-10
Authors: Danial Roshandel; Jennifer A Thompson; Rachael C Heath Jeffery; Danuta M Sampson; Enid Chelva; Terri L McLaren; Tina M Lamey; John N De Roach; Shane R Durkin; Fred K Chen Journal: Transl Vis Sci Technol Date: 2021-02-05 Impact factor: 3.283
Authors: Lorenzo Bianco; Alessandro Arrigo; Alessio Antropoli; Paola Carrera; Ivana Spiga; Maria Grazia Patricelli; Francesco Bandello; Maurizio Battaglia Parodi Journal: Am J Ophthalmol Case Rep Date: 2022-04-21