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Updated: Jul 8, 2026
09:16
Array Comparative Genomic Hybridization (Array CGH) for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
Genomic Copy Number Variants Associated With Strabismus and Amblyopia in the All of Us Research Program
Kyoung A Viola Lee1,2, Mary C Whitman1,3,4
1Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States.
Investigative Ophthalmology & Visual Science
|July 7, 2026
Summary
Copy number variants (CNVs) are linked to strabismus and amblyopia. These genetic variations implicate synaptic and neurodevelopmental pathways in the cause of these vision disorders.
Area of Science:
- Genetics
- Ophthalmology
- Genomic Medicine
Background:
- Strabismus and amblyopia are common childhood vision disorders with complex etiologies.
- Genetic factors are known to contribute to these conditions, but specific variants remain to be fully elucidated.
Purpose of the Study:
- To identify both rare and common copy number variants (CNVs) associated with strabismus and amblyopia.
- To investigate the role of specific CNVs in the genetic risk for these vision impairments.
Main Methods:
- A case-control association study utilizing whole-genome sequencing data from the All of Us Research Program.
- Analysis of structural variant calls to identify autosomal CNVs in individuals with strabismus and amblyopia compared to controls.
- Categorization of CNVs into rare (<1% frequency) and common (>1% frequency) based on population frequency.
Main Results:
- One rare CNV (MDGA2 deletion) and three common CNVs (CAMK2D, COG1, KMT2C) were associated with amblyopia.
- Three rare CNVs (PCDH15, GTF2H1, NKAIN3 deletions) and two common CNVs (TRANK1 deletion, GRK5 duplication) were associated with strabismus.
- Genes implicated in CNVs affect neuronal and synaptic functions, including GRK5 which interacts with CXCR4, crucial for oculomotor nerve guidance. A previously identified chr4 duplication was replicated in association with strabismus.
Conclusions:
- Copy number variants represent an additional genetic risk factor for strabismus and amblyopia.
- The findings underscore the importance of synaptic and neurodevelopmental pathways in the etiology of these vision disorders.
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