Less severe hereditary retinopathies can result from subtle genotypic variants
Bart P Leroy MD
Not all hereditary retinopathies show their typical, severe phenotype and maculopathy in some cases can be at the mild end of the disease’s spectrum, said Bart P Leroy MD, Ghent University Hospital, Ghent, Belgium.
“Mild end-of-the-spectrum retinal disease can result from pathogenic genetic variants with milder effects than the usual phenotype. The genotypic spectra of these conditions are also wider than we initially thought,” Dr Le Roy told the Retina 2020 meeting in Dublin Ireland, funded by the Irish patient-led charity, Fighting for Sight.
The diagnostic process in cases of suspected hereditary retinal dystrophies begins with asking patients the right questions in language they can understand about the nature of their visual complaints and the time of onset, he noted. Also important is drawing a pedigree and looking for potential causes for the disorder with specialised imaging. In addition, patients should undergo functional testing with psychophysics and electrophysiology. The clinical diagnosis should be confirmed with genotyping.
Ocular genetics has identified 307 genes for inherited retinal and optic neuropathy diseases, Dr Leroy said. He added that ocular genetics has come a long way in recent years. In particular, high-throughput molecular sequencing technology, such as whole exome sequencing, is rapidly replacing the older, Sanger sequencing.
In cases where the diagnosis is uncertain, the technology can be used to find the subtle variants of a suspect gene. The variants can include deep intronic variants in regulatory sequences, deep intronic mutations or subtle copy number variations. The molecular findings should be interpreted in the context of the clinical presentation, Dr Le Roy said.