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

doi:10.3346/jkms.2019.34.e161

Cited by 57 publications

(65 citation statements)

References 41 publications

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“…A number of prior studies have examined IRD cohorts. 4 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 Table 2 presents the most frequently involved genes in many of these published studies over the last 3 to 4 years. Obvious similarities exist in terms of genes affected across diverse geographic regions.…”

Section: Discussionmentioning

confidence: 99%

“…of Molecularly Diagnosed (No. of Genes) Most Frequently Implicated Genes Current study United Kingdom 4241 individuals from 3197 families (135 genes) By family: ABCA4 , USH2A , RPGR , PRPH2 , BEST1 ; by individual: ABCA4 , USH2A , RPGR , PRPH2 , RHO 2019 Khan 10 United Arab Emirates (children) 71 individuals (26 genes) ABCA4 , KCNV2 , CRB1 , CNGA3 Sharon et al 11 Israel 1369 families (129 genes) ABCA4 , USH2A , FAM161A , CNGA3 , EYS Holtan et al 12 Norway 207 patients (56 genes) ABCA4 , USH2A , BEST1 , RHO , RS1 Avela et al 13 Finland (children) 41 families (17 genes) RS1 , GUCY2D , RPGR Kim et al 14 Korea 38 individuals (24 genes) ABCA4 , EYS , PDE6B , USH2A , PDE6A , GUCY2D Tayebi et al 15 Iran 36 families (19 genes) ABCA4 , RPE65 , CERKL , RPGRIP1 2018 Motta et al 16 Brazil 400 individuals (66 genes) ABCA4 , CEP290 , USH2A , CRB1 , RPGR Wang et al 17 China 132 families (47 genes) USH2A , RPGR , CYP4V2 , ABCA4 , CRB1 , RHO 2017 <...>…”

Section: Discussionmentioning

confidence: 99%

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Genetic Basis of Inherited Retinal Disease in a Molecularly Characterized Cohort of More Than 3000 Families from the United Kingdom

et al. 2020

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Purpose In a large cohort of molecularly characterized inherited retinal disease (IRD) families, we investigated proportions with disease attributable to causative variants in each gene. Design Retrospective study of electronic patient records. Participants Patients and relatives managed in the Genetics Service of Moorfields Eye Hospital in whom a molecular diagnosis had been identified. Methods Genetic screening used a combination of single-gene testing, gene panel testing, whole exome sequencing, and more recently, whole genome sequencing. For this study, genes listed in the Retinal Information Network online resource ( https://sph.uth.edu/retnet/ ) were included. Transcript length was extracted for each gene (Ensembl, release 94). Main Outcome Measures We calculated proportions of families with IRD attributable to variants in each gene in the entire cohort, a cohort younger than 18 years, and a current cohort (at least 1 patient encounter between January 1, 2017, and August 2, 2019). Additionally, we explored correlation between numbers of families and gene transcript length. Results We identified 3195 families with a molecular diagnosis (variants in 135 genes), including 4236 affected individuals. The pediatric cohort comprised 452 individuals from 411 families (66 genes). The current cohort comprised 2614 families (131 genes; 3130 affected individuals). The 20 most frequently implicated genes overall (with prevalence rates per families) were as follows: ABCA4 (20.8%), USH2A (9.1%), RPGR (5.1%), PRPH2 (4.6%), BEST1 (3.9%), RS1 (3.5%), RP1 (3.3%), RHO (3.3%), CHM (2.7%), CRB1 (2.1%), PRPF31 (1.8%), MY07A (1.7%), OPA1 (1.6%), CNGB3 (1.4%), RPE65 (1.2%), EYS (1.2%), GUCY2D (1.2%), PROM1 (1.2%), CNGA3 (1.1%), and RDH12 (1.1%). These accounted for 71.8% of all molecularly diagnosed families. Spearman coefficients for correlation between numbers of families and transcript length were 0.20 ( P = 0.025) overall and 0.27 ( P = 0.017), –0.17 ( P = 0.46), and 0.71 ( P = 0.047) for genes in which variants exclusively cause recessive, dominant, or X-linked disease, respectively. Conclusions Our findings help to quantify the burden of IRD attributable to each gene. More than ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic Basis of Inherited Retinal Disease in a Molecularly Characterized Cohort of More Than 3000 Families from the United Kingdom

et al. 2020

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“…Adjacent variants (p.Thr546Asn and p.Trp548Leu) only mention ACHM as the phenotype of the patients, with no further information or pictures provided. 13,24 Mutations near that of patient D's variant (p.Thr436Ser) were classified as pathogenic (e.g., p.Val402Glu, p.Met442Lys, and p.Met455Val). 8,15,22 The phenotype's description of the first two mutations is imprecise, only stating that the patients had ACHM.…”

Section: Discussionmentioning

confidence: 99%

PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults

Varela

Ullah

Yousaf

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Genetic variation in PDE6C is associated with achromatopsia and cone dystrophy, with only a few reports of cone-rod dystrophy in the literature. We describe two pediatric and two adult patients with PDE6C related cone and cone-rod dystrophy and the first longitudinal data of a pediatric patient with PDE6C-related cone dystrophy. METHODS. This cohort of four patients underwent comprehensive ophthalmologic evaluation at the National Eye Institute's Ophthalmic Genetics clinic, including visual field testing, retinal imaging and electroretinogram (ERG). Next-generation sequencing-based genetic testing was performed and subsequent analysis of the variants was done through three-dimensional protein models generated by Phyre2 and Chimera. RESULTS. All cases shared decreased best-corrected visual acuity and poor color discrimination. Three of the four patients had a cone-rod dystrophy, presenting with an ERG showing decreased amplitude on both photopic and scotopic waveforms and a mild to moderately constricted visual field. One of the children was diagnosed with cone dystrophy, having a preserved peripheral field. The children had none to minor structural retinal changes, whereas the adults had clear macular dystrophy. CONCLUSIONS. PDE6C-related cone-rod dystrophy consists of a severe phenotype characterized by early-onset nystagmus, decreased best-corrected visual acuity, poor color discrimination, progressive constriction of the visual field, and night blindness. Our work contributes with valuable information toward understanding the visual prognosis and allelic heterogeneity of PDE6C-related cone and cone-rod dystrophy.

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“…The median age at examination was 40.0 years (range, . The mean follow-up duration was 3.1 years (range, [1][2][3][4][5][6][7][8][9][10][11][12]. According to their clinical history, 13 of 15 patients (86.7%) experienced night blindness as their first ocular symptom at a median age of 10.0 years (range, 5-47 years) and 9 of 15 patients (60.0%) were less than 10 years old at symptom onset.…”

Section: Demographicsmentioning

confidence: 99%

Clinical characteristics and disease progression of retinitis pigmentosa associated with PDE6B mutations in Korean patients

Kim

Song

et al. 2020

Sci Rep

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Due to the genotype–phenotype heterogeneity in retinitis pigmentosa (RP), molecular diagnoses and prediction of disease progression is difficult. This study aimed to report ocular and genetic data from Korean patients with PDE6B-associated RP (PDE6B-RP), and establish genotype–phenotype correlations to predict the clinical course. We retrospectively reviewed targeted next-generation sequencing or whole exome sequencing data for 305 patients with RP, and identified PDE6B-RP in 15 patients (median age, 40.0 years). Amongst these patients, ten previously reported PDE6B variants (c.1280G > A, c.1488del, c.1547T > C, c.1604T > A, c.1669C > T, c.1712C > T, c.2395C > T, c.2492C > T, c.592G > A, and c.815G > A) and one novel variant (c.712del) were identified. Thirteen patients (86.7%) experienced night blindness as the first symptom at a median age of 10.0 years. Median age at diagnosis was 21.0 years and median visual acuity (VA) was 0.20 LogMAR at the time of genetic analysis. Nonlinear mixed models were developed and analysis revealed that VA exponentially decreased over time, while optical coherence tomography parameters linearly decreased, and this was related with visual field constriction. A high proportion of patients with the c.1669C > T variant (7/9, 77.8%) had cystoid macular edema; despite this, patients with this variant did not show a higher rate of functional or structural progression. This study will help clinicians predict functional and structural progression in patients with PDE6B-RP.

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Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases

Cited by 57 publications

References 41 publications

Genetic Basis of Inherited Retinal Disease in a Molecularly Characterized Cohort of More Than 3000 Families from the United Kingdom

Genetic Basis of Inherited Retinal Disease in a Molecularly Characterized Cohort of More Than 3000 Families from the United Kingdom

PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults

Clinical characteristics and disease progression of retinitis pigmentosa associated with PDE6B mutations in Korean patients

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