TGFBI gene screening in Iranian TGFBI associated corneal dystrophies affected patients
Roxanne Jozaie1 , Fatemeh Suri2 *, Afrooz Moghaddasi3 , Bahar Safdari2 , Mohammad-Ali Javadi2 , Sepehr Feizi2 , Mozhgan Rezaei-Kanavi4 , Iman Salahshuri-Far5
- Department of biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Abstract: Mutations in transforming growth factor beta-induced (TGFBI) gene are responsible for developing multiple corneal dystrophies (CDs) including: granular corneal dystrophy type 1 (GCD1), granular corneal dystrophy type 2 (GCD2) or Avellino corneal dystrophy, lattice corneal dystrophy (LCD), Thiel-Behnke corneal dystrophy (TBCD), and Reis-Bücklers corneal dystrophy (RBCD). TGFBI-associated CDs, with an autosomal dominant mode of inheritance, belong to the epithelial-stromal category of CDs. In the present study, we aimed to investigate the TGFBI causative mutations in Iranian patients with different types of related CDs and evaluate their frequency and phenotype-genotype correlation in Iranian patients
Methods: Complete ophthalmic examinations were performed and finally 23 Iranian patients with various diagnosis of the TGFBI-associated CDs were selected. Blood samples were collected and genomic DNA was extracted from peripheral blood leukocytes using salting out protocol. Exons 4 and 12 of the TGFBI were amplified using polymerase chain reaction and subsequently sequenced by the Sanger method. The sequences were compared to reference sequence in order to identify sequence variations.
Results: Out of 23 patients, 50% were diagnosed with GCD1, 36.36% with LCD, and 13.64% with RBCD, according to the ophthalmologist diagnosis. Causative mutations were found in 91.3% (21/23) of the patients in exon 4 or 12 of the gene. Six previously known variations including p.Arg124Cys, p.Arg124His, p.Arg555Trp, p.Arg555Gln, p.Ala546Thr, and p.Ile522Asn were found among the Iranian patients. 90% of the identified mutations were located at amino acids Arg124 and Arg555 codons in exon 4 and 12, respectively.
Conclusion: To the best of our knowledge this is the first population-based TGFBI gene screening among the Iranian patients. It was obviously found that the Arg124 and Arg555 amino acids are hot spots for Iranian families with TGFBI-associated CDs as previously reported for the other populations. Therefore, sequencing of only two exons of TGFBI can solve the genetic testing of more than 90% of the Iranian families in a time and cost consuming manner
