Babak Emamalizadeh1, Yousef Daneshmandpour1,2, Somayeh Kazeminasb1, Ehsan Aghaei Moghadam3, Zahra Bahmanpour1,2, Elham Alehabib4, Somayeh Alinaghi4, Azadeh Doozandeh5, Minoo Atakhorrami6, Hossein Darvish7,8. 1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Department of Pediatrics, School of Medicine, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 4. Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5. Department of Ophthalmology, Torfeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 6. Department of Biology, Faculty of Basic Sciences, East Tehran Branch (Ghiamdasht), Islamic Azad University, Tehran, Iran. minooatakhorrami@yahoo.com. 7. Department of Medical Genetics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. darvish_mg@yahoo.com. 8. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran. darvish_mg@yahoo.com.
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.
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.
Authors: Fereshteh Chitsazian; Betsabeh Khoramian Tusi; Elahe Elahi; Heidar Amini Saroei; Mohammad H Sanati; Shahin Yazdani; Mohammad Pakravan; Navid Nilforooshan; Yadollah Eslami; Mohammad Ali Zare Mehrjerdi; Reza Zareei; Mahmood Jabbarvand; Ali Abdolahi; Ali R Lasheyee; Arash Etemadi; Behnaz Bayat; Mehdi Sadeghi; Mohammad M Banoei; Behnam Ghafarzadeh; Mohammad R Rohani; Akram Rismanchian; Yvonne Thorstenson; Mansoor Sarfarazi Journal: J Mol Diagn Date: 2007-07 Impact factor: 5.568
Authors: Sarah E Hunt; William McLaren; Laurent Gil; Anja Thormann; Helen Schuilenburg; Dan Sheppard; Andrew Parton; Irina M Armean; Stephen J Trevanion; Paul Flicek; Fiona Cunningham Journal: Database (Oxford) Date: 2018-01-01 Impact factor: 3.451
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