Whole-genome sequencing can significantly improve the diagnosis of complex inherited eye conditions, helping patients and families receive answers much earlier than is possible with standard genetic testing, a new study shows.
University of Leicester investigators Dr Mahmoud Fassad and Dr Mervyn Thomas led the study which combined detailed clinical information with whole-genome sequencing (WGS) data from Genomics England’s landmark 100,000 Genomes Project.
The study in NPJ Genomic Medicine on 20 May 2026 focused on infantile nystagmus and albinism, two genetically complex conditions that often affect vision from birth or early infancy.
Researchers analysed data from 473 affected people across 388 families, making it the largest cohort of its kind investigated using whole-genome sequencing.
The team identified a genetic cause in 46% of participants (218 individuals), including definitive diagnoses in 176 cases. Importantly, whole-genome sequencing uncovered disease-causing mutations that would have been missed by conventional gene-panel testing.
Among the findings, researchers discovered that 45 families carried mutations in 36 genes that were not included in standard diagnostic panels. Without genome-wide analysis, these diagnoses would likely have remained undetected.
The study also highlighted the importance of a pattern in the TYR gene known as the “cis YQ” haplotype. Frequently overlooked in routine testing, it emerged as the most common genetic cause of disease within the study cohort.
Dr Fassad said findings demonstrate the clinical value of comprehensive genomic testing for patients with complex inherited eye disease.
“These results show that using full genome testing can save patients months and even years of misery when it comes to diagnosing complex eye conditions,” he said. “Knowing the exact gene involved can alert doctors to related health issues such as significant refractive errors, squint (strabismus), and, in some cases, hearing loss and developmental delays.”
The researchers also explored links between genetic findings and clinical features. They found refractive errors and conditions associated with foveal hypoplasia were significantly more common among participants. Strabismus and neurodevelopmental features were also over-represented, providing further insight into how these disorders manifest.
Dr Thomas said the study revealed a level of genetic complexity that challenges current diagnostic approaches.
“This study showed that the genetic architecture of infantile nystagmus and albinism is far more complex than previously appreciated and therefore standard gene panels are simply not enough,” he said.
“The breadth of diagnoses found, including rare syndromes and dual diagnoses, makes a compelling case for whole-genome sequencing as the first-line diagnostic tool.”
Dr Thomas said obtaining a precise genetic diagnosis can improve clinical care, provide families with clearer information about inheritance patterns and future pregnancies, and help patients access emerging gene-targeted therapies and clinical research opportunities.
The findings add to growing evidence that whole-genome sequencing could play a larger role in ophthalmic practice, particularly for patients with rare inherited retinal and neuro-ophthalmic disorders where conventional testing may fail to provide answers.
