背景:SLC29A3基因,它编码核苷转运蛋白,主要位于细胞内膜。该基因的突变可以引起各种临床表现,包括H综合征,心肌硬化,Faisalabad组织细胞增生症,和胰岛素依赖型糖尿病的色素沉着多毛症。这项研究的目的是介绍两名患有H综合征的伊朗患者,并描述SLC29A3基因中的一种新的开始丢失突变。
方法:在本研究中,我们采用全外显子组测序(WES)作为一种方法,在一名16岁女孩及其8岁哥哥中鉴定有助于H综合征发展的遗传变异.这些兄弟姐妹是伊朗家庭的一部分,父母是近亲。为了证实鉴定出的变异体的致病性,我们利用了计算机工具和交叉引用的各种数据库来确认它的新颖性。此外,我们进行了一项共隔离研究,并通过Sanger测序验证了受影响患者父母中变异体的存在.
结果:在我们的研究中,我们发现了一个新的起始丢失突变(c.2T>A,p.Met1Lys)在SLC29A3基因中,在两个患者中都发现了。使用Sanger测序的共分离分析证实该变体是从亲本遗传的。为了评估这种突变的潜在致病性和新颖性,我们查阅了各种数据库。此外,我们使用生物信息学工具来预测突变的SLC29A3蛋白的三维结构。进行这些分析的目的是提供对所鉴定的突变对SLC29A3蛋白的结构和功能的功能影响的有价值的见解。
结论:我们的研究为支持SLC29A3基因突变与H综合征之间的关联提供了越来越多的证据。与SLC29A3相关疾病的分子分析对于理解变异范围和提高对H综合征的认识至关重要。最终目标是促进早期诊断和适当治疗。在先证者中发现这种新颖的双等位基因变体进一步强调了利用遗传测试方法的重要性,如WES,作为具有这种特殊情况的个人的可靠诊断工具。
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.
CONCLUSIONS: 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.