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Mutational Analysis of Cyp1b1 Gene in Iranian Pedigrees With Glaucoma Reveals Known and Novel Mutations Publisher Pubmed



Emamalizadeh B1 ; Daneshmandpour Y1, 2 ; Kazeminasb S1 ; Aghaei Moghadam E3 ; Bahmanpour Z1, 2 ; Alehabib E4 ; Alinaghi S4 ; Doozandeh A6 ; Atakhorrami M7 ; Darvish H5, 8
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Department of Pediatrics, School of Medicine, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Medical Genetics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
  6. 6. Department of Ophthalmology, Torfeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Department of Biology, Faculty of Basic Sciences, East Tehran Branch (Ghiamdasht), Islamic Azad University, Tehran, Iran
  8. 8. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran

Source: International Ophthalmology Published:2021


Abstract

Purpose: Primary congenital glaucoma (PCG) (OMIM#231,300) can be caused by pathogenic sequence variations in CYP1B1, LTBP2, MYOC and PXDN genes. The purpose of this study was to investigate mutations in the CYP1B1 gene in families affected with primary congenital glaucoma (PCG) using linkage analysis and Sanger sequencing. Methods: A total number of four families with nine affected PCG patients during six months were included in this study. The mutations were identified by homozygosity mapping to find the linked loci and then direct sequencing of all coding exons, the exon–intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA obtained from affected family members and their parents. Moreover, bioinformatic tools were applied to study mutation effect on protein structure and function. Results: A total of four mutations were identified, and three of these were novel. Two were missense mutations: One was truncating mutation, and the other was an in-frame deletion. Mutations in CYP1B1 could fully explain the PCG phenotype in all of the patients. Also, the bioinformatic study of the mutations showed the structure of the protein is affected, and it is well conserved among similar species. Conclusion: In this study, we identified 4 CYP1B1 mutations, 3 of which were novel. In silico analysis of identified mutations confirmed their molecular pathogenicity. A similar analysis will help understand the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG. Clinical trials registration: Not relevant © 2021, The Author(s), under exclusive licence to Springer Nature B.V.
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