Genetic Diagnosis in Congenital Cataracts

Study Overview
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Brief Summary
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The prediction of genetic risk in congenital cataract patients has great clinical significance. In this trial, the investigators aim to screen the causative variants from 115 unrelated bilateral congenital cataract patients enrolled consecutively, describe novel and recurrent variants, analyze the factors affecting genetic diagnostic yield, and explore potential phenotype-genotype correlation.

Detailed Description
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Determining whether the disease is hereditary and the precise genetic cause of congenital cataract has great clinical significance in guiding genetic counseling and improving clinical care pathway. Varying among studies, genetic causes account for 8.3-85% of congenital cataracts because of the difference in ethnic background, genetic screening techniques used, the percentage of patients with bilateral cataracts, with a family history, and with syndromic disease. A phenotype-genotype correlation may be used to predict the causative genes, and the involvement of other tissues and organs based on the appearance of the lens. In addition, it can be used to improve our understanding of lens biology. A phenotype-genotype correlation is difficult to establish because of the genotypic and phenotypic heterogeneity of congenital cataracts. In this trail, the investigators aim to screen the causative variants from 115 unrelated bilateral congenital cataract patients enrolled consecutively, describe novel and recurrent variants, analyze the factors affecting genetic diagnostic yield, and explore potential phenotype-genotype correlation. Facial and anterior eye segment photographs, pre- and post-operative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data.

Official Title
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Genetic Diagnosis and Phenotype-genotype Correlation in a Large Chinese Cohort of Congenital Cataracts

Conditions
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Congenital Cataract

Intervention / Treatment
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* Procedure: Ophthalmic examination
* Genetic: Whole-exome sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant with bilateral congenital cataract; Have signed a consent form. . Exclusion Criteria: 1. The participant not identified with congenital cataract; 2. The participant with unilateral congenital cataract. -

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bilateral congenital cataract probands who were consecutively enrolled<br> | Procedure: Ophthalmic examination<br>* Facial photographs of the participants were obtained at the time of enrolment. Pre- and post-operative anterior eye segment photographs were obtained under diffuse, direct focal and retro illumination. Clinical data, including basic information, family history, and comprehensive pre- and post-operative ophthalmic examination findings, were recorded.<br>Genetic: Whole-exome sequencing<br>* Performing whole-exome sequencing and bioinformatics analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whether the participant has pathogenic genes |  | 2 years | 
| Type of the cataracts | The cataracts were categorized into 17 groups (Membranous cataract, Thin and fibrotic nuclear cataract, Nuclear cataract, Zonular cataract, Pulverulent cataract, Pocket-like cataract, Ant egg cataract, Cerulean cataract, Coronary cataract, Coralliform cataract, Cortical cataract, Sutural cataract, Anterior subcapsular cataract, Anterior polar cataract, Posterior subcapsular cataract, Posterior polar cataract, Total cataract) | before surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whether the participant has family history |  | 2 years | 
| The symmetricity of the type of cataract |  | before surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Congenital cataract, Genetic diagnosis, Phenotype-genotype correlation