Identification of a novel mutation in the SDCCAG8 gene in an Iranian family with Bardet-Biedl Syndrome

Identification of a novel mutation in the SDCCAG8 gene in an Iranian family with Bardet-Biedl Syndrome
Zahra Bahmanpour ,¹ Yousef Daneshmandpour ,² Parisa Moeinian ,³ Sedigheh Sadat Mortazavi ,⁴ Somayeh Kazeminasab,⁵ Babak Emamalizadeh ,^6,*
1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3. Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
4. Division of Genetics, Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
5. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
6. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Introduction: Bardet–Biedl syndrome is known as a rare ciliopathic human genetic disorder. Typically, BBS follows the autosomal recessive pattern of inheritance, however, it has also been reported as an oligogenic inheritance. The prevalence of BBS among the populations varies from 1 in 13500 to 1 in 160000. BBS is a genetically heterogeneous disorder with a wide spectrum of clinical manifestations including loss of vision, obesity, extra fingers or toes abnormalities of the genitalia, intellectual disability, and several other features that make its diagnosis and management more challenging. RetNet reports 18 genes that cause BBS and each of these genes has had numerous known mutations. Genetic studies suggesting that SDCCAG8 (also called BBS16) gene mutations are a major cause of BBS. This gene plays an essential role in the formation of cell polarity, epithelial lumen, and ciliogenesis and is also a prominent element in the Hedgehog signaling pathway.
Methods: In this section, we investigated the consanguineous Iranian family members with BBS. Whole-exome sequencing (WES) 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: The sequential analysis revealed 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.
Conclusion: 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.
Keywords: Bardet–Biedl syndrome (BBS); SDCCAG8; Whole-exome sequencing; Novel mutation, Bioinformatics