Laboratory of Human Molecular Genetics, Faculty of Medicine, Magida Boulila Street, 3029 Sfax, University of Sfax, Tunisia.
Center of Human Genetics, Institute of Pathology and Genetics, Biopark Charleroi Brussels South. Rue Adrienne Bolland 8. Aéropole de Gosselies, B - 6041 Gosselies, Belgium.
Gene. 2018 Sep 10;671:28-35. doi: 10.1016/j.gene.2018.05.112. Epub 2018 Jun 1.
Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most frequent genetic disorder of the kidneys, is characterized by a typical presenting symptoms include cysts development in different organs and a non-cysts manifestations. ADPKD is caused by mutations in PKD1 or PKD2 genes. In this study, we aimed to search for molecular causative defects among PKD1 and PKD2 genes. Eighteen patients were diagnosed based on renal ultrasonography and renal/extra-renal manifestations. Then, Sanger sequencing was performed for PKD1 and PKD2 genes. Multiplex Ligation dependent Probe Amplification method (MLPA) methods was performed for both PKD genes. Mutational analysis of the PKD2 gene revealed the absence of variants and no deletions or duplications of both PKD genes were detected. But three novels mutations i.e. p.S463C exon 7; c. c.11156+2T>C IVS38 and c.8161-1G>A IVS22 and two previously reported c.1522T>C exon 7 and c.412C>T exon 4 mutations in the PKD1 gene were detected. Bioinformatics tools predicted that the novel variants have a pathogenic effects on splicing machinery, pre-mRNA secondary structure and stability and protein stability. Our results highlighted molecular features of Tunisian patients with ADPKD and revealed novel variations that can be utilized in clinical diagnosis and in the evaluation of living kidney donor. To the best of our knowledge, this is the first report of Autosomal Polycystic Kidney Disease in Tunisia.
常染色体显性多囊肾病（ADPKD）是最常见的肾脏遗传疾病，其特征为典型的临床表现包括不同器官的囊肿形成和非囊肿表现。ADPKD是由 PKD1 或 PKD2 基因突变引起的。在本研究中，我们旨在搜索 PKD1 和 PKD2 基因中的分子致病缺陷。根据肾脏超声和肾外表现诊断了 18 名患者。然后，对 PKD1 和 PKD2 基因进行 Sanger 测序。对 PKD2 基因进行多重连接依赖性探针扩增（MLPA）方法。PKD2 基因的突变分析显示没有变体，并且没有检测到两个 PKD 基因的缺失或重复。但是，在 PKD1 基因中检测到三个新的突变，即 p.S463C 外显子 7；c. c.11156+2T>C IVS38 和 c.8161-1G>A IVS22 以及两个先前报道的 c.1522T>C 外显子 7 和 c.412C>T 外显子 4 突变。生物信息学工具预测，新的变体对剪接机制、前体 mRNA 二级结构和稳定性以及蛋白质稳定性具有致病性影响。我们的结果突出了突尼斯 ADPKD 患者的分子特征，并揭示了可用于临床诊断和活体供肾评估的新变异。据我们所知，这是突尼斯首例常染色体多囊肾病的报告。
