Mutation in DOP1B is cause of Peters anomaly in a pedigree with three affected individuals
Ensieh Darbari1 , Davood Zare-Abdollahi 2 , Afagh Alavi 2 , Mozhgan Rezaei Kanavi 3 , Sepehr Feizi 4 , Seyed Bagher Hosseini5 , Alireza Baradaran-Rafii 3 , Hamid Ahmadieh 4 , Shohreh Issazadeh-Navikas6 , Elahe Elahi 1 *
- School of Biology, College of Science, University of Tehran, Tehran, Iran
- Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ocular Pathology Unit, Central Eye Bank of Iran, Tehran, Iran
- Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, Copenhagen Biocentre, University of Copenhagen, 2200 Copenhagen, Denmark
Abstract: Peters anomaly (PA) is a form of ASD which itself is clinically heterogeneous. PA is characterized by central corneal opacity, and iridocorneal or corneolenticular adhesion. Many disease causing genes relating to PA are not identified. we performed whole exome sequencing of three PA patients affected in a pedigree.
Methods: Slit lamp biomicroscopy and ultrasound biomicroscopy were performed for definitive diagnosis. Exome sequencing was done on the DNA of all three patients. The candidate causative gene was identified. Candidate gene expression was analyzed in ocular tissues related to PA in human adult and embryo by Real Time PCR.
Results: Inheritance of PA was autosomal recessive. After appropriate filtration a homozygous variation c.G4978A (p.V1660I) in DOP1B gene was the only common variation between patients. This variation was reported only in heterozygous state in different database. Expression of DOP1B was shown in all adult and embryonic lens, iris, cornea, sclera, and retina tissues that were tested
Conclusion: It is the first time c.G4978A in DOP1B gene is reported in homozygous state. P.V1660 is conserved among mammalian and birds. DOP1B is one of the member of Dopey family. Members of the Dopey gene family have been shown to have roles in development in other organisms. Evidence of DOP1B expression in various PA-relevant eye tissues, which to the best of our knowledge is shown here for the first time, is consistent with it may have a Probable role in eye development
