GUCY2D mutations in a Chinese cohort with autosomal dominant cone or cone–rod dystrophies

Jiang, Feng; Xu, Ke; Zhang, Xiaohui; Xie, Yue; Bai, Fengge; Yang, Li

doi:10.1007/s10633-015-9509-7

Cited by 11 publications

(13 citation statements)

References 21 publications

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“…Leber congenital amaurosis (LCA), the most severe form of IRD, appears as congenital or infantile‐onset vision loss caused by early onset rod and/or cone photoreceptor cell degeneration . Cone‐rod dystrophy (CRD) presents as a loss of central vision and/or peripheral vision . In addition to the extensive clinical overlap among IRDs, genetic overlap further complicates the molecular diagnosis of this group of diseases.…”

Section: Introductionmentioning

confidence: 99%

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Chen

Lin

Lee³

et al. 2020

Clinical Exper Ophthalmology

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Background: Inherited retinal dystrophy (IRD) is a group of irreversible retinal degenerative disorders with significant genotypic and phenotypic heterogeneity, which cause difficulty in making a precise clinical diagnosis.Furthermore, the mutation spectrum of IRD in Taiwan remains unknown. Therefore, our study focused on investigating the spectrum of mutations among Taiwanese families with IRD using targeted exome sequencing (TES) technology. Methods: We recruited a total of 60 unrelated Taiwanese families with IRD; most of them were retinitis pigmentosa. We employed TES to investigate 284 candidate genes. Bioinformatics analysis, Sanger sequencing-based cosegregation testing, and computational assessment were performed to validate each mutation and its pathogenicity. The genotype-phenotype correlation was analysed in all patients with mutations defined in the guidelines provided by the American College of Medical Genetics. Results: We successfully identified genetic causes in 32 families (detection rate of 53.3%). Among them, 16 had a sporadic inheritance (16/36, 44.4%); eight had an autosomal recessive inheritance (8/14, 57.1%); four had an autosomal dominant inheritance (4/5, 80%); four had an X-linked inheritance (4/5, 80%). Among 38 pathological mutations in 19 known genes, 20 mutations are reported here for the first time. Novel mutation spectrum and genotypephenotype correlations were revealed as well. Conclusion: Here we achieved a detection rate of 53.3% and elucidated the mutation spectrum in Taiwanese families with IRD for the first time. The results indicated that CYP4V2 and USH2A might be the most common pathogenic genes in IRD patients in Taiwan. K E Y W O R D Sinherited retinal dystrophy, mutations spectrum, Taiwanese population, targeted exome sequencing

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Section: Introductionmentioning

confidence: 99%

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Chen

Lin

Lee³

et al. 2020

Clinical Exper Ophthalmology

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“…In a previous report of a Chinese cohort, Jiang et al reported nine unrelated probands with GUCY2D-RD ascertained from 74 probands with CORD (9/74, 12.2%) and seven of 15 ADCORD families had GUCY2D-RD (7/15, 46.7%). 37 The proportion of GUCY2D-RD in molecularly confirmed ADCORD was 34.6% in a UK cohort and 29.4% in a French cohort. 5,48 Given these results, the prevalence of GUCY2D-RD for CORD in Japan was not as high as that in other populations in Asia or Europe; however, GUCY2D-RD is a major cause of the ADCORD.…”

Section: Discussionmentioning

confidence: 87%

“… 11 – 13 , 16 , 56 These findings are consistent with previous reports of AD GUCY2D -CORD. 20 , 34 , 37 , 38 Therefore, comprehensive clinical investigations, including electrophysiological assessments, are essential for the diagnosis and monitoring of GUCY2D -RD.…”

Section: Discussionmentioning

confidence: 99%

“…19,27 Since then, more than 200 variants in the GUCY2D gene have been associated with a wide range of different phenotypes of IRDs. 9,19,20,[28][29][30][31][32][33][34][35][36][37][38][39] Sharon et al reported that 88% of GUCY2D-associated retinal disorder (GUCY2D-RD) is AR-LCA, whereas pathogenic heterozygous missense GUCY2D variants cause AD-CORD. 20 In that, pathogenic GUCY2D variants are one of the major causes of LCA, as well as a major cause of AD-CORD.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder

Liu

Fujinami

Kuniyoshi

et al. 2020

Trans. Vis. Sci. Tech.

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To determine the clinical and genetic characteristics of patients with GUCY2Dassociated retinal disorder (GUCY2D-RD). Methods: Fifteen patients from 12 families with inherited retinal disorder (IRD) and harboring GUCY2D variants were ascertained from 730 Japanese families with IRD. Comprehensive ophthalmological examinations, including visual acuity (VA) measurement, retinal imaging, and electrophysiological assessment were performed to classify patients into three phenotype subgroups; macular dystrophy (MD), cone-rod dystrophy (CORD), and Leber congenital amaurosis (LCA). In silico analysis was performed for the detected variants, and the molecularly confirmed inheritance pattern was determined (autosomal dominant/recessive [AD/AR]). Results: The median age of onset/examination was 22.0/38.0 years (ranges, 0-55 and 1-73) with a median VA of 0.80/0.70 LogMAR units (ranges, 0.00-1.52 and 0.10-1.52) in the right/left eye, respectively. Macular atrophy was identified in seven patients (46.7%), and two had diffuse fundus disturbance (13.3%), and six had an essentially normal

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“…For the review of previously published clinical data on GUCY2D , a MEDLINE/PubMed search was performed on 1 May 2020 (gucy2d eye, gucy2d dystrophy) and all publications with available clinical data have been included for further analysis (20 out of 112 publications) [ 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. For statistical analysis and creation of graphs, Graph Pad Prism 6 as well as R version 3.6.0 were used.…”

Section: Methodsmentioning

confidence: 99%

GUCY2D-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data

Neubauer

Hahn

Birtel

et al. 2022

Genes

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To report the clinical phenotype and associated genotype of a European patient cohort with GUCY2D-related autosomal-dominant (AD) cone–/cone–rod dystrophy (COD/CORD), we retrospectively analyzed 25 patients (17 female, range 12–68) with GUCY2D-related AD-COD/CORD from three major academic centers in Europe and reviewed the previously published data of 148 patients (visual acuity (VA), foveal thickness, age of first symptoms, and genetic variant). Considering all the patients, the onset of first symptoms was reported at a median age of 7 years (interquartile range 5–19 years, n = 78), and mainly consisted of reduced VA, photophobia and color vision abnormality. The disease showed a high degree of inter-eye symmetry in terms of VA (n = 165, Spearman’s ρ = 0.85, p < 0.0001) and foveal thickness (Spearman’s ρ = 0.96, n = 38, p < 0.0001). Disease progression was assessed by plotting VA as a function of age (n = 170). A linear best-fit analysis suggested a loss of 0.17 logMAR per decade (p < 0.0001). We analyzed the largest cohort described so far (n = 173), and found that the most common mutations were p.(Arg838Cys) and p.(Arg838His). Furthermore, the majority of patients suffered severe vision loss in adulthood, highlighting a window of opportunity for potential intervention. The emerging patterns revealed by this study may aid in designing prospective natural history studies to further define endpoints for future interventional trials.

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GUCY2D mutations in a Chinese cohort with autosomal dominant cone or cone–rod dystrophies

Abstract: The GUCY2D mutations were frequent in Chinese families with autosomal dominant cone or cone-rod dystrophies. All mutations were found in exon 13, which should be given priority during mutation screening analysis.

Cited by 11 publications

References 21 publications

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder

GUCY2D-Related Retinal Dystrophy with Autosomal Dominant Inheritance—A Multicenter Case Series and Review of Reported Data

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