2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Retrospective Review of Genetic Testing and Variant Reclassification in Patients With Congenital Cataracts

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A study reviewed genetic testing results in patients with congenital cataracts and reclassified variants in accordance with the ACMG-AMP 2015 sequence variant interpretation guidelines. The study included 52 patients with diverse ethnic backgrounds and both syndromic and non-syndromic cataracts. The most common variant classification initially was a Variant of Uncertain Significance (VUS), but after reinterpretation, many variants were downgraded to Likely Benign or Benign. The diagnostic yield was highest for whole exome sequencing (WES) at 57%. The study found inconsistencies in the tests ordered, with over 50% of patients having no diagnostic result. The authors suggest considering WES as the test of choice, especially in syndromic cataract presentations. They also recommend periodic reinterpretation of results to potentially move test reports from inconclusive to positive or negative. Further research is needed to better understand gene-disease relationships and establish disease-specific rules for variant interpretation to improve the accuracy of genetic testing results in individuals with congenital cataracts.<br /><br />Congenital cataracts are opacities of the lens in the eye that are present at birth. They can be unilateral or bilateral and have various causes, including infectious or genetic factors. The incidence of congenital cataracts is approximately 3 in 10,000 individuals, but it may be underreported. Genetic testing for congenital cataracts has been limited in the past due to cost and lack of insurance coverage. However, the availability of commercially sponsored panels has led to an increase in panel testing, particularly for retinal dystrophies. The genetic influence on congenital cataracts is not fully understood, and the best testing strategies have not yet been determined. GO analysis, which identifies over- or under-representation of ontological terms in gene lists, may be helpful in discovering novel gene-disease relationships in conditions such as congenital cataracts. Further research is needed to fully explore the genetics of congenital cataracts and improve the use of genetic testing in diagnosing the condition.

Asset Subtitle

Presenting Author - Alexander Ing, MS, CGC; Co-Author - Andy Drackley, MS, CGC; Co-Author - Kevin Zhang, MD PhD; Co-Author - Kai Lee Yap, PhD; Co-Author - Hanta Ralay-Ranaivo, PhD; Co-Author - Jennifer Rossen, MD;

Meta Tag

array CGH

Exome sequencing

Eye disorders

Genetic Testing

NextGen Sequencing

Co-Author Andy Drackley, MS, CGC

Co-Author Kevin Zhang, MD PhD

Co-Author Kai Lee Yap, PhD

Co-Author Hanta Ralay-Ranaivo, PhD

Co-Author Jennifer Rossen, MD

Presenting Author Alexander Ing, MS, CGC

Keywords

genetic testing

congenital cataracts

ACMG-AMP 2015

sequence variant interpretation

ethnic backgrounds

syndromic cataracts

Variant of Uncertain Significance

whole exome sequencing

diagnostic yield

gene-disease relationships