Voretigene Neparvovec for the Treatment of RPE65-associated Retinal Dystrophy: Consensus and Recommendations from the Korea RPE65-IRD Consensus Paper Committee

Jinu Han(Jinu Han),Kwangsic Joo(Kwangsic Joo),Ungsoo Samuel Kim(Ungsoo Samuel Kim),Se Joon Woo(Se Joon Woo),Eun Kyoung Lee(Eun Kyoung Lee),Joo Yong Lee(Joo Yong Lee),Tae Kwann Park(Tae Kwann Park),San 대한안과학회 2023 Korean Journal of Ophthalmology Vol.37 No.2

Mutations in the RPE65 gene, associated with Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitispigmentosa, gained growing attention since gene therapy for patients with RPE65-associated retinal dystrophy is available inclinical practice. RPE65 gene accounts for a very small proportion of patients with inherited retinal degeneration, especiallyAsian patients. Because RPE65-associated retinal dystrophy shares common clinical characteristics, such as early-onset severenyctalopia, nystagmus, low vision, and progressive visual field constriction, with retinitis pigmentosa by other geneticmutations, appropriate genetic testing is essential to make a correct diagnosis. Also, fundus abnormalities can be minimal inearly childhood, and the phenotype is highly variable depending on the type of mutations in RPE65-associated retinal dystrophy,which makes a diagnostic difficulty. The aim of this paper is to review the epidemiology of RPE65-associated retinaldystrophy, mutation spectrum, genetic diagnosis, clinical characteristics, and voretigene neparvovec, a gene therapy productfor the treatment of RPE65-related retinal dystrophy.

CCDC41 is required for ciliary vesicle docking to the mother centriole

Joo, Kwangsic,Kim, Chang Gun,Lee, Mi-Sun,Moon, Hyun-Yi,Lee, Sang-Hee,Kim, Mi Jeong,Kweon, Hee-Seok,Park, Woong-Yang,Kim, Cheol-Hee,Gleeson, Joseph G.,Kim, Joon National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.15

<P>The initiation of primary cilium assembly entails the docking of ciliary vesicles presumably derived from the Golgi complex to the distal end of the mother centriole. Distal appendages, which anchor the mother centriole to the plasma membrane, are thought to be involved in the docking process. However, little is known about the molecular players and mechanisms that mediate the vesicle–centriole association. Here we report that coiled-coil domain containing 41 (CCDC41) is required for the docking of ciliary vesicles. CCDC41 specifically localizes to the distal end of the mother centriole and interacts with centrosomal protein 164 (Cep164), a distal appendage component. In addition, a pool of CCDC41 colocalizes with intraflagellar transport protein 20 (IFT20) subunit of the intraflagellar transport particle at the Golgi complex. Remarkably, knockdown of CCDC41 inhibits the recruitment of IFT20 to the centrosome. Moreover, depletion of CCDC41 or IFT20 inhibits ciliogenesis at the ciliary vesicle docking step, whereas intraflagellar transport protein 88 (IFT88) depletion interferes with later cilium elongation steps. Our results suggest that CCDC41 collaborates with IFT20 to support the vesicle–centriole association at the onset of ciliogenesis.</P>

Clinical and Genetic Characteristics of Retinal Capillary Hemangioblastoma in Korean Patients

Sang Ha Lee(Sang Ha Lee),Kyu Hyung Park(Kyu Hyung Park),Se Joon Woo(Se Joon Woo),Sang Jun Park(Sang Jun Park),Kwangsic Joo(Kwangsic Joo) 대한안과학회 2022 Korean Journal of Ophthalmology Vol.36 No.6

Purpose: We investigated the clinical features of Korean patients with retinal capillary hemangioblastoma (RCH) and genetic variants of the von Hippel-Lindau (VHL) gene. Methods: A retrospective analysis was performed on patients with RCH from 2003 to 2021 at Seoul National University Bundang Hospital. Sporadic and hereditary RCH associated with VHL disease were classified based on the specific tumors and family history. Clinical features, including the location and number of RCH and bilateral involvement, were investigated. Multiplex ligation-dependent probe amplification and direct sequencing targeting the VHL gene were performed for six RCH cases associated with VHL disease. Results: A total of 18 patients (23 eyes) were enrolled in this study. The mean age at diagnosis was 37 ± 15 years. Twelve patients had hereditary RCH associated with VHL disease, and six patients had sporadic RCH. All five patients with bilateral RCH were clinically diagnosed with VHL disease, and 13 patients had unilateral RCH. Juxtapapillary RCH was only observed in patients with VHL. The most common complication of RCH was the epiretinal membrane, followed by the subretinal fluid. Pathogenic variants were identified in four patients. All three patients with type 1 VHL had the well-known missense mutation p.Glu70Lys, and one patient with type 2 VHL had the nonsense mutation p.Trp88Ter. Conclusions: In Korean patients with RCH, bilateral involvement and juxtapapillary RCH are highly likely to be associated with VHL disease. Because RCH may be the first clinical manifestation in patients with VHL, active genetic testing of the VHL gene and systemic evaluation are required.

Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases

Kim, Min Seok,Joo, Kwangsic,Seong, Moon-Woo,Kim, Man Jin,Park, Kyu Hyung,Park, Sung Sup,Woo, Se Joon The Korean Academy of Medical Sciences 2019 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.34 No.21

<P><B>Background</B></P><P>Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea.</P><P><B>Methods</B></P><P>Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD.</P><P><B>Results</B></P><P>Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. <I>ABCA4</I> was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n = 1), and cone dystrophy (n = 1). In particular, mutations in <I>EYS</I> were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the <I>ABCA4</I> gene with an autosomal recessive trait.</P><P><B>Conclusion</B></P><P>This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients.</P>

Congenital Stationary Night Blindness due to Novel TRPM1 Gene Mutations in a Korean Patient

Yun Jeong Lee,Kwangsic Joo,Moon-Woo Seong,Kyu Hyung Park,Sung Sup Park,Se Joon Woo 대한안과학회 2020 Korean Journal of Ophthalmology Vol.34 No.2

Subfoveal Nodule Affecting Visual Prognosis in Coats Disease

Hyunchul Jeong,Sang Jun Park,Kwangsic Joo 대한안과학회 2024 Korean Journal of Ophthalmology Vol.38 No.1

Purpose: To investigate the characteristics of subfoveal nodules in Korean patients with Coats disease and their association with visual outcomes Methods: A retrospective analysis was conducted within the medical records of patients with stage 2B or 3A1 Coats disease, including clinical features, imaging, presence of either a subfoveal nodule or macular fibrosis, and visual outcome. Results: Twelve patients were present with stage 2B or 3A1 Coats disease, and nine patients (75%) presented with subfoveal nodule. Between the group without subfoveal nodule and the group with subfoveal nodule, there were no significant differences in age (mean, 14.0 ± 1.7 years vs. 27.7 ± 21.8 years; p = 0.482), sex (all men), stage of the disease (stage 2B: three patients vs. eight patients, p > 0.999; stage 3A1: none vs. one patient, p > 0.999), extension of retinal exudation (mean, 7.7 hours vs. 4.1 hours; p = 0.209) and peripheral telangiectasia (mean, 3.7 hours vs. 4.2 hours; p = 0.727), and follow-up duration (mean, 65.0 months vs. 46.1 months; p = 0.600). There were significantly more patients with severe visual loss (≤20 / 200) among the patients with subfoveal nodule (none vs. seven patients, p = 0.045), and the cause for severe visual loss was macular fibrosis in all cases. Macular fibrosis developed significantly more frequently in the patients with subfoveal nodule (none vs. seven = patients, p = 0.045). Conclusions: This study is the first study covering the analysis of subfoveal nodules in Korean patients with Coats disease. The existence of a subfoveal nodule at the initial diagnosis serves as an indicator predicting the development of macular fibrosis and a less favorable visual outcome in the patients with Coats disease. A multicenter study with a larger patient pool and further studies toward the therapeutic approach for the subfoveal nodule and macular fibrosis are needed.