Microarray-based mutation detection and phenotypic characterization in Korean patients with retinitis pigmentosa

Kim, Cinoo,Kim, Kwang Joong,Bok, Jeong,Lee, Eun-Ju,Kim, Dong-Joon,Oh, Ji Hee,Park, Sung Pyo,Shin, Joo Young,Lee, Jong-Young,Yu, Hyeong Gon Molecular Vision 2012 Molecular vision Vol.18 No.-

<P><B>Purpose</B></P><P>To evaluate microarray-based genotyping technology for the detection of mutations responsible for retinitis pigmentosa (RP) and to perform phenotypic characterization of patients with pathogenic mutations.</P><P><B>Methods</B></P><P>DNA from 336 patients with RP and 360 controls was analyzed using the GoldenGate assay with microbeads containing 95 previously reported disease-associated mutations from 28 RP genes. Mutations identified by microarray-based genotyping were confirmed by direct sequencing. Segregation analysis and phenotypic characterization were performed in patients with mutations. The disease severity was assessed by visual acuity, electroretinography, optical coherence tomography, and kinetic perimetry.</P><P><B>Results</B></P><P>Ten RP-related mutations of five RP genes (PRP3 pre-mRNA processing factor 3 homolog [<I>PRPF3</I>], rhodopsin [<I>RHO</I>], phosphodiesterase 6B [<I>PDE6B</I>], peripherin 2 [<I>PRPH2</I>], and retinitis pigmentosa 1 [<I>RP1</I>]) were identified in 26 of the 336 patients (7.7%) and in six of the 360 controls (1.7%). The p.H557Y mutation in <I>PDE6B</I>, which was homozygous in four patients and heterozygous in nine patients, was the most frequent mutation (2.5%). Mutation segregation was assessed in four families. Among the patients with missense mutations, the most severe phenotype occurred in patients with p.D984G in <I>RP1</I>; less severe phenotypes occurred in patients with p.R135W in <I>RHO</I>; a relatively moderate phenotype occurred in patients with p.T494M in <I>PRPF3</I>, p.H557Y in <I>PDE6B</I>, or p.W316G in <I>PRPH2</I>; and a mild phenotype was seen in a patient with p.D190N in <I>RHO</I>.</P><P><B>Conclusions</B></P><P>The results reveal that the GoldenGate assay may not be an efficient method for molecular diagnosis in RP patients with rare mutations, although it has proven to be reliable and efficient for high-throughput genotyping of single-nucleotide polymorphisms. The clinical features varied according to the mutations. Continuous effort to identify novel RP genes and mutations in a population is needed to improve the efficiency and accuracy of the genetic diagnosis of RP.</P>

Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa

Kim, Kwang Joong,Kim, Cinoo,Bok, Jeong,Kim, Kyung-Seon,Lee, Eun-Ju,Park, Sung Pyo,Chung, Hum,Han, Bok-Ghee,Kim, Hyung-Lae,Kimm, Kuchan,Yu, Hyeong Gon,Lee, Jong-Young Molecular Vision 2011 Molecular vision Vol.17 No.-

<P><B>Purpose</B></P><P>To determine the spectrum and frequency of rhodopsin gene (<I>RHO</I>) mutations in Korean patients with retinitis pigmentosa (RP) and to characterize genotype–phenotype correlations in patients with mutations.</P><P><B>Methods</B></P><P>The <I>RHO</I> mutations were screened by direct sequencing, and mutation prevalence was measured in patients and controls. The impact of missense mutations to RP was predicted by segregation analysis, peptide sequence alignment, and in silico analysis. The severity of disease in patients with the missense mutations was compared by visual acuity, electroretinography, optical coherence tomography, and kinetic visual field testing.</P><P><B>Results</B></P><P>Five heterozygous mutations were identified in six of 302 probands with RP, including a novel mutation (c.893C>A, p.A298D) and four known mutations (c.50C>T, p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; and c.1040C>T, p.P347L). The allele frequency of missense mutations was measured in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic. Among the patients with the missense mutations, we observed the most severe phenotype in patients with p.P347L, less severe phenotypes in patients with p.Y178C or p.A298D, and a relatively moderate phenotype in a patient with p.T17M.</P><P><B>Conclusions</B></P><P>The results reveal the spectrum of <I>RHO</I> mutations in Korean RP patients and clinical features that vary according to mutations. Our findings will be useful for understanding these genetic spectra and the genotype–phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy.</P>

Original Articles : The Anti-angiogenic Effect of Chlorogenic Acid on Choroidal Neovascularization

( Cinoo Kim ),( Hyeong Gon Yu ),( Joon Hong Sohn ) 대한안과학회 2010 Korean Journal of Ophthalmology Vol.24 No.3

Purpose: To evaluate the inhibitory effect of chlorogenic acid on laser-induced choroidal neovascularization (CNV) in a rat model. Methods: Intraperitoneal injection of chlorogenic acid (10 mg/kg) was inititated one day prior to laser photocoagulation and continued for eight days. Eyes were removed 14 days after laser photocoagulation. Fluorescein angiography was employed at seven and 14 days to assess the CNV lesions, and histological examination was performed. Quantification of CNV size and leakage were performed both in histological sections and fluorescein angiography in order to compare the inhibitory effects of chlorogenic acid on CNV with the results of the control. Results: Histological analysis showed no significant difference in CNV size between the treated and control groups. However, CNV leakage on fluorescein angiography had significantly decreased in the chlorogenic acid-treated group at 14 days after laser photocoagulation compared with that of the control group. In addition, CNV size on fluorescein angiography had significantly decreased in the treated group at seven and 14 days. Conclusions: These results suggest that chlorogenic acid has anti-angiogenic effects on CNV and may be useful as an inhibitor in the treatment or prevention of neovascular age-related macular degeneration.

Association of p.P347L in the rhodopsin gene with early-onset cystoid macular edema in patients with retinitis pigmentosa

Kim, Cinoo,Chung, Hum,Yu, Hyeong Gon Informa Healthcare 2012 Ophthalmic genetics Vol.33 No.2

<P><I>Purpose</I>: To describe early-onset cystoid macular edema (CME) in a family with retinitis pigmentosa (RP) due to the p.P347L in the rhodopsin gene (<I>RHO</I>).</P><P><I>Methods</I>: All affected family members, including a 44-year-old mother and four children in their teens (two daughters, 17 and 15 years old, and two sons, 13 and 11 years old), have a mutation of p.P347L in <I>RHO</I>. Funduscopy, Goldmann perimetry, spectral domain optical coherence tomography (SD-OCT) and electroretinogram (ERG) were performed in all affected members to assess the retinal anatomy and function.</P><P><I>Results</I>: The mother had very poor visual acuity of light perception in both eyes, and marked foveal atrophy was observed via SD-OCT. Although the macular appearance in the funduscopy looked unremarkable in the four children, SD-OCT revealed bilateral CME in all the children. The rod response in ERG was extinguished and the cone response was decreased in all children.</P><P><I>Conclusion</I>: The results present the possibility that CME in RP patients may be associated with a specific genotype such as the p.P347L in <I>RHO</I>. We speculate that the severe visual prognosis of this mutation may be related to early-onset CME, as shown in this family. However, further investigation in more RP patients with this mutation and CME will be needed.</P>

Diagnostic and predictive methods for a Niemann-Pick disease type B patient with ocular involvement

Kim, Cinoo,Jeong, Jinho,Yu, Hyeong Gon Wiley (John WileySons) 2010 Journal of inherited metabolic disease Vol.33 No.5

대기오염이 자살, 우울증 및 정신질환에 미치는 영향

강신우(Cinoo Kang),송인성(In Sung Song),장정주(Jeongju Jang),서다은(Da Eun Seo),김호(Ho Kim) 서울대학교 보건환경연구소 2020 보건학논집 Vol.57 No.1

외상성 섬모체해리로 인한 저안압황반병증 환자에서 가스주입술 및 냉동치료를 병행한 유리체절제술로 치료한 1예

김신우,유형곤,Cinoo Kim,Hyeong Gon Yu 대한안과학회 2006 대한안과학회지 Vol.47 No.10

Purpose: To report a case of hypotony maculopathy caused by traumatic cyclodialysis and treated by vitrectomy combined with gas tamponade and cryotherapy. Methods: A 35-year-old man with hypotony maculopathy caused by traumatic cyclodialysis was unsuccessfully treated with conservative medical therapy, laser photocoagulation, and direct cyclopexy. The intraocular pressure (IOP) was 2 mm Hg and the vision was counting finger with chorioretinal folds. Vitrectomy combined with gas tamponade and cryotherapy was performed without lens surgery 5 months after trauma. Results: After vitrectomy, fundus photograph and optical coherence tomography revealed complete loss of preoperative chorioretinal folds. The visual acuity improved to 0.3 and IOP was maintained within a normal range during the 24 month follow-up. Conclusions: This case shows that vitrectomy combined with gas tamponade and cryotherapy is effective for the treatment of traumatic cyclodialysis with persistent hypotony, probably without lens surgery.

The joint effects of leisure activity and alcohol drinking on mild cognitive impairment (MCI) in Korean adults: Analysis of the 2019 Korea Community Health Survey

Jieun Min,Cinoo Kang,Wasunkar Shreeya,Ho Kim 서울대학교 보건환경연구소 2021 보건학논집 Vol.58 No.2

맥락막신생혈관의 광역학치료후 발생한 장액성 망막박리

김신우,정흠,허장원,Cinoo Kim,Hum Chung,Jang Won Heo 대한안과학회 2007 대한안과학회지 Vol.48 No.10

Purpose: To quantify the development and resolution of serous retinal detachment in patients with choroidal neovascularization (CNV) following photodynamic therapy (PDT). Methods: Six eyes of five patients who developed serous retinal detachment two days after PDT were included in this study. Retinal thickness was measured by optical coherence tomography (OCT) before PDT, and at two days, seven days, and three weeks after PDT. The number of PDT and the greatest linear dimension (GLD) of the CNV lesion were recorded. Results: Serous retinal detachment was demonstrated on OCT at two days after PDT. Retinal elevation increased significantly from 313.2 m before PDT to 640.7 m two days after PDT (P<0.01); elevation and decreased to 303.2 m seven days after PDT, and decreased to 223.4 m three weeks after PDT. The mean number of PDT treatments 2.0 (range: 1~3), and the mean GLD before PDT was 3122.81275.9 m. Conclusions: This study suggest that serous retinal detachment in patients with CNV may develop following PDT but may also resolve spontaneously seven days after PDT.

초고령자의 백내장 수술시 술후 시력결과에 영향을 미치는 인자

김신우,권지원,위원량,이진학-,한영근,Cinoo Kim,M,D,Ji Won Kwon,M,D,Won Ryang Wee,M,D,Jin Hak Lee,M,D,-,Young Keun Han,M,D 대한안과학회 2007 대한안과학회지 Vol.48 No.7

Purpose: To analyze the outcome of cataract surgery and to determine factors influencing the postoperative visual acuity in patients aged 85 years and older. Methods: The best corrected visual acuity before and 3 months after cataract surgery in patients aged 85 years and older was measured. Age, sex, diabetes mellitus, hypertension, astigmatism, corneal endothelial cell count, ocular comorbidity, and intraoperative complication were analyzed to determine which factors influence the postoperative visual acuity. Results: The postoperative visual acuity improved in 87% of patients, and a visual acuity of 20/40 or better was achieved in 56% of patients. Posterior capsular rupture and zonular dialysis were found as intraoperative complications in 16% of patients. Multiple regression analysis was used to determine which factors influence the postoperative visual acuity; age(p=0.009), ocular comorbidity (p=0.009), and intraoperative complication (p=0.010) were significantly associated with postoperative visual acuity. Conclusions: The postoperative visual acuity following cataract surgery in patients aged 85 years and older improved in 87% of patients, and old age, ocular comorbidity, and intraoperative complication were predictors of a poorer visual outcome.