A novel start-loss mutation of the SLC29A3 gene in a consanguineous family with H syndrome: clinical characteristics, in silico analysis and literature review.
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引用次数: 0
Abstract
Background: The SLC29A3 gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation in SLC29A3 gene.
Methods: In this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing.
Results: In our study, we identified a novel start-loss mutation (c.2T > A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein.
Conclusion: Our study contributes to the expanding body of evidence supporting the association between mutations in the SLC29A3 gene and H syndrome. The molecular analysis of diseases related to SLC29A3 is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.
一个患有 H 综合征的近亲结婚家族中的 SLC29A3 基因新型起始缺失突变:临床特征、硅分析和文献综述。
背景:SLC29A3 基因编码一种核苷转运蛋白,主要位于细胞内膜。该基因突变可导致多种临床表现,包括 H 综合征、骨质硬化症、费萨拉巴德组织细胞增生症和伴有胰岛素依赖型糖尿病的色素性多毛症。本研究的目的是介绍两名伊朗 H 综合征患者,并描述 SLC29A3 基因的一种新型起始丢失突变:在这项研究中,我们采用了全外显子组测序(WES)方法,以确定导致一名 16 岁女孩和她 8 岁哥哥患 H 综合征的基因变异。这对兄妹是伊朗近亲家庭的成员。为了确认所发现变异的致病性,我们使用了体内工具,并交叉比对了各种数据库,以确认其新颖性。此外,我们还进行了共分离研究,并通过桑格测序验证了受影响患者的父母中存在该变异体:结果:在我们的研究中,我们在两名患者的 SLC29A3 基因中发现了一个新的起始缺失突变(c.2T > A, p.Met1Lys)。利用桑格测序法进行的共分离分析证实,该变异是由父母遗传的。为了评估该变异的潜在致病性和新颖性,我们查阅了各种数据库。此外,我们还利用生物信息学工具预测了突变 SLC29A3 蛋白的三维结构。进行这些分析的目的是为了深入了解所发现的突变对 SLC29A3 蛋白结构和功能的影响:我们的研究为越来越多的证据支持 SLC29A3 基因突变与 H 综合征之间的关联做出了贡献。对 SLC29A3 相关疾病的分子分析对于了解 H 综合征的变异范围和提高人们对 H 综合征的认识至关重要,其最终目的是促进早期诊断和适当治疗。在受试者中发现这种新型双倍变体进一步强调了利用基因检测方法(如 WES)作为可靠的诊断工具对患有这种特殊疾病的个体进行诊断的重要性。
期刊介绍:
BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.