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Background: To identify the mutational spectrum in a Chinese cohort with congenital cataracts. Methods: Probands (n = 164) with congenital cataracts and their affected or unaffected available family members were recruited for clinical examinations and panel‐based next‐generation sequencing, then classified into a cohort for further mutational analysis. Results: After recruitment (n = 442; 228 males and 214 females), 49.32% (218/442) of subjects received a clinical diagnosis of congenital cataracts, and 56.88% (124/218) of patients received a molecular diagnosis. Eighty‐four distinct variants distributed among 43 different genes, including 42 previously reported variants and 42 novel variants, were detected, and 49 gene variants were causally associated with patient phenotypes; 27.37% of variants (23/84) were commonly detected in PAX6, GJA8 and CRYGD, and the three genes covered 33.06% of cases (41/124) with molecular diagnosis. The majority of genes were classified as genes involved in nonsyndromic congenital cataracts (19/43, 44.19%) and were responsible for 56.45% of cases (70/124). The majority of functional and nucleotide changes were missense variants (53/84, 63.10%) and substitution variants (74/84, 88.10%), respectively. Nine de novo variants were identified. Conclusion: This study provides a reference for individualized genetic counseling and further extends the mutational spectrum of congenital cataracts. [ABSTRACT FROM AUTHOR]

Purpose: To provides the clinical and genetic characteristics of a series of Chinese patients with X‐linked juvenile retinoschisis (XLRS) through multimodal imaging and next‐generation sequencing. Methods: Thirty patients (60 eyes) from 29 unrelated families of Chinese origin with XLRS were screened using multigene panel testing, and underwent a complete clinical evaluation. All variants identified in this study and reported in the Human Gene Mutation Database were analysed. Results: Twenty‐five distinct variants in the retinoschisin gene were identified, of which eight were novel, and one was de novo. Missense mutations were the most prevalent type, and mutation hot spot was localized in the discoidin domain. The mean Snellen best‐corrected visual acuity was 0.28 ± 0.17. Of all eyes presenting with schisis, 92.86% had lamellar schisis and 62.5% had peripheral schisis. Schisis changes mostly involved inner and outer nuclear layers. X‐linked juvenile retinoschisis (XLRS) patients had a high incidence of complications, and peripheral schisis was a risk factor for it. No obvious genotype–phenotype association was observed. Conclusion: This study provides comprehensive analyses of the genetic and clinical characteristics of XLRS in a cohort of Chinese patients. The fourth de novo mutation in RS1 was identified. And we show that XLRS has a wide spectrum of clinical characteristics; hence, molecular diagnosis is crucial for its diagnosis, differential diagnosis and genetic counselling. Peripheral schisis is a risk factor for the high incidence of complications, and no clear genotype–phenotype correlations were found. [ABSTRACT FROM AUTHOR]

Background: The retinoid isomerohydrolase RPE65 has received considerable attention worldwide since a successful clinical gene therapy was approved in 2017 as the first treatment for vision loss associated with RPE65-mediated inherited retinal disease. Identifying patients with RPE65 mutations is a prerequisite to assessing the patients' eligibility to receive RPE65-targeted gene therapies, and it is necessary to identify individuals who are most likely to benefit from gene therapies. This study aimed to investigate the RPE65 mutations frequency in the Chinese population and to determine the genetic and clinical characteristics of these patients.Results: Only 20 patients with RPE65 mutations were identified, and RPE65 mutations were determined to be the 14th most common among all patients with genetic diagnoses. Ten novel variants and two hotspots associated with FAP were identified. A literature review revealed that a total of 57 patients of Chinese origin were identified with pathogenic mutations in the RPE65 gene. The mean best Snellen corrected visual acuity was worse (mean 1.3 ± 1.3 LogMAR) in patients older than 20 years old than in those younger than 15 years old (0.68 ± 0.92 LogMAR). Bone spicule-like pigment deposits (BSLPs) were observed in six patients; they were older than those without BSLP and those with white-yellow dots. Genotype-phenotype analysis revealed that truncating variants seem to lead to a more severe clinical presentation, while best corrected visual acuity testing and fundus changes did not correlate with specific RPE65 variants or mutation types.Conclusions: This study provides a detailed clinical-genetic assessment of patients with RPE65 mutations of Chinese origin. These results may help to elucidate RPE65 mutations in the Chinese population and may facilitate genetic counseling and the implementation of gene therapy in China. [ABSTRACT FROM AUTHOR]

Purpose: To explore an early, rapid and precise diagnosis of Stickler syndrome type I (STL1) and to enrich the spectrum of COL2A1 mutations in the Chinese population, which is poorly studied at present. Methods: In the current study, we analysed 115 patients with high myopia by next‐generation sequencing and identified five STL1 patients from four unrelated Chinese families. The clinical features of all patients were reviewed in detail. Results: Four variants of COL2A1 were identified, including two novel variants (c.1435delG and c.184delG) and two previously reported variants (c.1221+1G>A and c.1030C>T). Three variants caused premature termination codons which were common in STL1. In addition, we proposed a new diagnostic tactic to improve early diagnostics of STL1 in patients. Conclusion: In this study, our findings expanded the spectrum of COL2A1 mutations with two novel variants and provided a new diagnostic tactic for reference, which was of great significance. Precise diagnosis on the basis of clinical manifestations and genetic testing will become the gold standard to diagnose inherited ocular disorders or syndromes in the future. [ABSTRACT FROM AUTHOR]