Genetic testing for Granular Corneal Dystrophy type1 in Malta uncovers the causative variant in the transforming growth factor beta induced gene

Abstract

Introduction: Granular corneal dystrophy (GCD) is a condition causing significant visual impairment . It is generally inherited in an autosomal dominant fashion and is phenotypically bilateral, non-inflammatory and progressive. Multiple allelic mutations in the transforming growth factor beta induced (TGFBI) gene produce various phenotypes. The aim of this research project was to determine the molecular genetics and mode of inheritance present in a cohort of Maltese patients who are members of the same family that phenotypically exhibit GCD type1. Methods: A complete ophthalmological examination of eight consenting Maltese individuals who have been clinically diagnosed with GCD was performed. Genomic DNA from all subjects was extracted from mouthwash samples. Gene sequencing of the TGFBI gene was carried out to identify the mutation(s) present in these Maltese patients. Results: Eight patients showed patterns of crumb- like corneal anterior stromal lesions. Five out of the eight samples collected were analysed. All the sequenced samples revealed a nucleotide missense mutation in chromosome 5q31, namely a nucleotide change of cytosine being replaced with thymine within exon 12. This caused the amino acid arginine to be replaced with tryptophan at codon 555. By analysing the family tree we could confirm the mode of inheritance. This was further confirmed by the sequencing results. Conclusion: This study is the first genetic analysis study carried out on Maltese patients that phenotypically exhibit corneal dystrophy. This is the first stepping stone towards understanding the genetic variations present within our population, making it easier for clinicians to identify and provide proper management to subjects at risk. Disclosures: Faculty Research Funding Committee, Faculty of Medicine and Surgery