Zahra Bahmanpour1,2,3, Yousef Daneshmandpour1,2, Somayeh Kazeminasab2, Soudabeh Khalil Khalili2, Elham Alehabib4, Marjan Chapi4, Mohsen Soosanabadi5, Hossein Darvish6,7, Babak Emamalizadeh8,9. 1. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5. Department of Medical Genetics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. 6. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran. Darvish_mg@yahoo.com. 7. Department of Medical Genetics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Darvish_mg@yahoo.com. 8. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Emamalizadeh_b@yahoo.com. 9. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Emamalizadeh_b@yahoo.com.
Abstract
PURPOSE: Bardet-Biedl syndrome (BBS: OMIM 209,900) is a rare ciliopathic human genetic disorder that affects many parts of the body systems. BBS is a genetically heterogeneous disorder with a wide spectrum of clinical manifestations which makes its diagnosis and management more challenging. RetNet reports 18 genes that cause BBS and each of genes has had several known mutations. Genetic studies suggesting that serologically defined colon cancer antigen 8 (SDCCAG8) gene mutations are a major cause of BBS. MATERIALS AND METHODS: In this section, we investigated the consanguineous Iranian family members with BBS. Whole-exome sequencing and Sanger sequencing, were performed to screen and confirm the suspicious pathogenic mutations. The identified mutation was investigated using bioinformatics tools to predict the effect of the mutation on protein structure. RESULTS: Sequential analysis identified a novel splice site mutation c.1221 + 2 T > A in the SDCCAG8 gene in BBS patients. Structure-based approaches have predicted significant structural alterations in SDCCAG8 protein. CONCLUSIONS: This study was conducted to show the aberrant alternative splicing as one of the single splicing mutations identified can cause BBS by affecting the function of SDCCAG8 protein.
PURPOSE: Bardet-Biedl syndrome (BBS: OMIM 209,900) is a rare ciliopathic human genetic disorder that affects many parts of the body systems. BBS is a genetically heterogeneous disorder with a wide spectrum of clinical manifestations which makes its diagnosis and management more challenging. RetNet reports 18 genes that cause BBS and each of genes has had several known mutations. Genetic studies suggesting that serologically defined colon cancer antigen 8 (SDCCAG8) gene mutations are a major cause of BBS. MATERIALS AND METHODS: In this section, we investigated the consanguineous Iranian family members with BBS. Whole-exome sequencing and Sanger sequencing, were performed to screen and confirm the suspicious pathogenic mutations. The identified mutation was investigated using bioinformatics tools to predict the effect of the mutation on protein structure. RESULTS: Sequential analysis identified a novel splice site mutation c.1221 + 2 T > A in the SDCCAG8 gene in BBS patients. Structure-based approaches have predicted significant structural alterations in SDCCAG8 protein. CONCLUSIONS: This study was conducted to show the aberrant alternative splicing as one of the single splicing mutations identified can cause BBS by affecting the function of SDCCAG8 protein.
Authors: A B Abdulla; Ahmed Al Muntasir Niloy; Tazin Afrose Shah; Sunil Kumar Biswas; A Khan Imran; Khaled Mahbub Murshed; Mashrafi Ahmed Journal: Mymensingh Med J Date: 2009-01
Authors: Muhammad Ajmal; Muhammad Imran Khan; Kornelia Neveling; Ali Tayyab; Sulman Jaffar; Ahmed Sadeque; Humaira Ayub; Nasir Mahmood Abbasi; Moeen Riaz; Shazia Micheal; Christian Gilissen; Syeda Hafiza Benish Ali; Maleeha Azam; Rob W J Collin; Frans P M Cremers; Raheel Qamar Journal: Mol Vis Date: 2013-03-21 Impact factor: 2.367