"Using advanced gene sequencing technologies, we firstly scanned for regions of DNA shared by all patients before analysing a single common region for the disease gene. From this we pinpointed STRA6, a gene responsible for transporting vitamin A into cells."
Working with Dr Hui Sun and Dr Riki Kawaguchi of the University of California, the research team went on to show that the genetic mutation identified in these patients significantly impairs the ability of STRA6 to transport vitamin A into the cells. And consequently, the amount of vitamin A needed to support normal eye development in the embryo is lacking.
The research funded by the National Children's Research Centre at Our Lady's Children's Hospital in Dublin and the Health Research Board in Ireland has resulted in significant advances in the understanding of individual genes that can cause anophthalmia, microphthalmia, and coloboma, and it also adds important diagnostic criteria to the field of general eye malformations.
"Changes in the DNA sequence of STRA6 have previously been shown to give rise to Matthew-Wood syndrome, a severe developmental disorder that includes eye malformations," explained Jillian Casey, UCD Health Sciences, University College Dublin, the first author on the scientific paper which was part of her PhD.
"At present, only patients with Matthew-Wood Syndrome are considered for STRA6 genetic testing. Our findings show that alterations in the STRA6 gene can also give rise to isolated eye malformations and suggest that patients with eye defects of unknown cause should also be considered for STRA6 testing."
Having identified the novel genetic basis of these eye defects in the Irish population, the scientists now aim to translate the findings into clinical practice. This will involve developing and introducing a genetic test to the diagnostic laboratory at the National Centre for Medical Genetics (NCMG).
The molecular lab
|Contact: Dominic Martella|
University College Dublin