A novel c.980C&gt;G variant in <i>OAT</i> results in identifiable gyrate atrophy phenotype associated with retinal detachment in a young female

Many forms of childhood glaucoma have been associated with underlying genetic changes, and variants in many genes have been described. Currently, testing is variable as there are no widely accepted guidelines for testing. This systematic review aimed to summarize the literature describing genetic changes and testing practices in childhood glaucoma. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) 2020 guidelines and registered with Prospero (ID CRD42023400467). A comprehensive review of Pubmed, Embase, and Cochrane databases was performed from inception through March 2, 2023 using the search terms: (glaucoma) AND (pediatric OR childhood OR congenital OR child OR infant OR infantile) AND (gene OR genetic OR genotype OR locus OR genomic OR mutation OR variant OR test OR screen OR panel). Information was extracted regarding genetic variants including genotype-phenotype correlation. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 1,916 records screened, 196 studies met inclusion criteria and 53 genes were discussed. Among study populations, mean age±SD at glaucoma diagnosis was 8.94±9.54 years and 50.4% were male. The most common gene discussed was CYP1B1, evaluated in 109 (55.6%) studies. CYP1B1 variants were associated with region and population-specific prevalence ranging from 5% to 86% among those with primary congenital glaucoma. MYOC variants were discussed in 31 (15.8%) studies with prevalence up to 36% among patients with juvenile open angle glaucoma. FOXC1 variants were discussed in 25 (12.8%) studies, which demonstrated phenotypic severity dependent on degree of gene expression and type of mutation. Overall risk of bias was low; the most common domains of bias were selection and comparability. Numerous genes and genetic changes have been associated with childhood glaucoma. Understanding the most common genes as well as potential genotype-phenotype correlation has the potential to improve diagnostic and prognostic outcomes for children with glaucoma.

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Multimodal imaging and genetic screening in Mexican patients with Gyrate Atrophy. Identification of novel OAT pathogenic variants.

Díazceballos-García,

Matsui,

Miranda

et al. 2024

Preprint

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Purpose Description of retinal phenotype by structural and functional testing, ornithine plasma levels and mutational data of OAT gene in patients with Gyrate Atrophy (GA). Methods Ophthalmologic examination, fundus photography (CFP), autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann perimetry (GP), full-field electroretinogram (ffERG) and chromatic perimetry (CP) testing were performed. Ornithine plasma levels were measured. Sanger sequencing mutational analysis of the coding exons and exon-intron junctions of the OAT gene were analyzed. Results Twelve eyes of seven Mexican patients with GA were included. CFF showed peripheric patches of chorioretinal atrophy; FAF revealed peripheric oval areas of hypoautofluorescence; SD-OCT exhibited outer retinal tubulations in 58%, cystoid macular edema in 50%, epiretinal membrane in 42%, foveoschisis and staphyloma in 17%, and hyperreflective deposits in 100% of the eyes; GP showed constricted visual fields in 100% of the eyes; ffERG revealed preserved photopic response in 17% and preserved scotopic response in 17% of the eyes; CP exposed a deficit in generalized response of rods and cones in 100% of the eyes. Mean ornithine plasma levels were 509.5 µmol/L. One patient with genetic confirmation of GA had normal ornithine plasma levels (48 µmol/L). Molecular findings in OAT gene detected two novel pathogenic variants: c.796 C > T (p.Gln266*) and c.721_722dupCC (p.Asp242ArgfsTer6). Conclusion This study provides new information regarding functional and structural diagnosis in patients with GA, expands the understanding of retinal phenotype in patients with GA, reports two novel mutations and presents the first case of GA confirmed by genetic testing with normal ornithine levels.

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A novel c.980C>G variant in OAT results in identifiable gyrate atrophy phenotype associated with retinal detachment in a young female

Cited by 3 publications

References 17 publications

The genetics and disease mechanisms of rhegmatogenous retinal detachment

The genetics and disease mechanisms of rhegmatogenous retinal detachment

Genetic changes and testing associated with childhood glaucoma: A systematic review

Multimodal imaging and genetic screening in Mexican patients with Gyrate Atrophy. Identification of novel OAT pathogenic variants.

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