Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Int Ophthalmol. 2021 Feb;41(2):389-397. doi: 10.1007/s10792-020-01588-x. Epub 2020 Sep 14.
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.
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.
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.
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.
Bardet-Biedl 综合征（BBS：OMIM 209,900）是一种罕见的纤毛病人类遗传疾病，影响身体多个系统。BBS 是一种遗传异质性疾病，临床表现广泛，使其诊断和管理更加具有挑战性。RetNet 报告了 18 个导致 BBS 的基因，每个基因都有几个已知的突变。遗传研究表明，血清定义的结肠癌抗原 8（SDCCAG8）基因突变是 BBS 的主要原因。
在这一部分，我们研究了具有 BBS 的伊朗近亲家庭成员。进行了全外显子组测序和 Sanger 测序，以筛选和确认可疑的致病突变。使用生物信息学工具研究鉴定出的突变，以预测突变对蛋白质结构的影响。
序列分析在 BBS 患者的 SDCCAG8 基因中鉴定出一个新的剪接位点突变 c.1221 + 2 T > A。基于结构的方法预测了 SDCCAG8 蛋白的显著结构改变。
本研究旨在表明异常的选择性剪接是导致 BBS 的单一剪接突变之一，可通过影响 SDCCAG8 蛋白的功能引起 BBS。
