Genetic Diagnosis in Congenital Cataracts

Congenital Cataract Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05782452
• Other study ID #: 2020KYPJ004
• Status: Completed
• Start date: January 1, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: March 2023
• Source: Zhongshan Ophthalmic Center, Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Gender: All
• Age group: 0 Years to 18 Years

Eligibility

Inclusion Criteria:

1. The participant with bilateral congenital cataract;

2. Have signed a consent form. .

Exclusion Criteria:

1. The participant not identified with congenital cataract; 2. The participant with unilateral congenital cataract.

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Related Conditions & MeSH terms

• Cataract
• Congenital Cataract

Intervention

Procedure:
• Ophthalmic examination
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.

Genetic:
• Whole-exome sequencing
Performing whole-exome sequencing and bioinformatics analysis.

Locations

Country	Name	City	State
China	Zhongshan Ophthalmic Center, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Zhongshan Ophthalmic Center, Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (11)

Aldahmesh MA, Khan AO, Mohamed JY, Hijazi H, Al-Owain M, Alswaid A, Alkuraya FS. Genomic analysis of pediatric cataract in Saudi Arabia reveals novel candidate disease genes. Genet Med. 2012 Dec;14(12):955-62. doi: 10.1038/gim.2012.86. Epub 2012 Aug 30. — View Citation

Chen J, Ma Z, Jiao X, Fariss R, Kantorow WL, Kantorow M, Pras E, Frydman M, Pras E, Riazuddin S, Riazuddin SA, Hejtmancik JF. Mutations in FYCO1 cause autosomal-recessive congenital cataracts. Am J Hum Genet. 2011 Jun 10;88(6):827-838. doi: 10.1016/j.ajhg — View Citation

Feinmann J. The BMJ Christmas appeal 2016-17: changing children's lives through cataract surgery. BMJ. 2016 Dec 15;355:i6650. doi: 10.1136/bmj.i6650. No abstract available. — View Citation

Gillespie RL, O'Sullivan J, Ashworth J, Bhaskar S, Williams S, Biswas S, Kehdi E, Ramsden SC, Clayton-Smith J, Black GC, Lloyd IC. Personalized diagnosis and management of congenital cataract by next-generation sequencing. Ophthalmology. 2014 Nov;121(11): — View Citation

Haargaard B, Wohlfahrt J, Fledelius HC, Rosenberg T, Melbye M. Incidence and cumulative risk of childhood cataract in a cohort of 2.6 million Danish children. Invest Ophthalmol Vis Sci. 2004 May;45(5):1316-20. doi: 10.1167/iovs.03-0635. — View Citation

Kandaswamy DK, Prakash MVS, Graw J, Koller S, Magyar I, Tiwari A, Berger W, Santhiya ST. Application of WES Towards Molecular Investigation of Congenital Cataracts: Identification of Novel Alleles and Genes in a Hospital-Based Cohort of South India. Int J — View Citation

Musleh M, Hall G, Lloyd IC, Gillespie RL, Waller S, Douzgou S, Clayton-Smith J, Kehdi E, Black GC, Ashworth J. Diagnosing the cause of bilateral paediatric cataracts: comparison of standard testing with a next-generation sequencing approach. Eye (Lond). 2 — View Citation

Ng D, Thakker N, Corcoran CM, Donnai D, Perveen R, Schneider A, Hadley DW, Tifft C, Zhang L, Wilkie AO, van der Smagt JJ, Gorlin RJ, Burgess SM, Bardwell VJ, Black GC, Biesecker LG. Oculofaciocardiodental and Lenz microphthalmia syndromes result from dist — View Citation

Rechsteiner D, Issler L, Koller S, Lang E, Bahr L, Feil S, Ruegger CM, Kottke R, Toelle SP, Zweifel N, Steindl K, Joset P, Zweier M, Suter AA, Gogoll L, Haas C, Berger W, Gerth-Kahlert C. Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract — View Citation

Scott MH, Hejtmancik JF, Wozencraft LA, Reuter LM, Parks MM, Kaiser-Kupfer MI. Autosomal dominant congenital cataract. Interocular phenotypic variability. Ophthalmology. 1994 May;101(5):866-71. doi: 10.1016/s0161-6420(94)31246-2. — View Citation

Shiels A, Hejtmancik JF. Biology of Inherited Cataracts and Opportunities for Treatment. Annu Rev Vis Sci. 2019 Sep 15;5:123-149. doi: 10.1146/annurev-vision-091517-034346. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Whether the participant has pathogenic genes		2 years
Primary	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	Whether the participant has family history		2 years
Secondary	The symmetricity of the type of cataract		before surgery