Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar, Imam Abdulrahman Bin Faisal University , Dammam , Saudi Arabia.
Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University , Dammam , Saudi Arabia.
Ren Fail. 2019 Nov;41(1):842-849. doi: 10.1080/0886022X.2019.1655453.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and enlargement and dysfunction of the kidneys. The Consortium of Radiologic Imaging Studies of the Polycystic Kidney Disease (CRISP) cohort revealed that 89.1% had either a or mutation. Of the CRISP patients with a genetic cause detected, mutations in accounted for 85%, while mutations in the accounted for the remaining 15%. Here, we report exome sequencing of 16 Saudi patients diagnosed with ADPKD and 16 ethnically matched controls. Exome sequencing was performed using combinatorial probe-anchor synthesis and improved DNA Nanoballs technology on BGISEQ-500 sequencers (BGI, China) using the BGI Exome V4 (59 Mb) Kit. Identified variants were validated with Sanger sequencing. With the exception of GC-rich exon 1, we obtained excellent coverage of (mean read depth = 88) including both duplicated and non-duplicated regions. Of nine patients with typical ADPKD presentations (bilateral symmetrical kidney involvement, positive family history, concordant imaging, and kidney function), four had protein truncating mutations, one had a missense mutation, and one had a mutation. These variants have not been previously observed in the Saudi population. In seven clinically diagnosed ADPKD cases but with atypical features, no or mutations were identified, but rare predicted pathogenic heterozygous variants were found in cystogenic candidate genes including , and . Mutations in PKD1 and PKD2 are the most common cause of ADPKD in Saudi patients with typical ADPKD. ADPKD: Autosomal dominant polycystic kidney disease; : Cystic fibrosis transmembrane conductance regulator; : Epidermal growth factor; MCIC: Mayo Clinic Imaging Classification; PKD: Polycystic kidney disease; : Tuberous sclerosis complex 2.
常染色体显性遗传性多囊肾病（ADPKD）的特征是肾脏囊肿进行性发展以及肾脏增大和功能障碍。放射影像学多囊肾病研究联合会（CRISP）队列研究显示，89.1%的患者要么携带 要么携带 突变。在 CRISP 患者中，检测到的遗传病因中， 突变占 85%，而 突变占其余的 15%。在这里，我们报告了 16 名沙特诊断为 ADPKD 的患者和 16 名种族匹配的对照者的外显子组测序结果。使用组合探针-锚合成和改良 DNA 纳米球技术，在 BGISEQ-500 测序仪（BGI，中国）上进行外显子组测序，使用 BGI 外显子组 V4（59Mb）试剂盒。使用 Sanger 测序对鉴定出的变体进行验证。除 GC 丰富的外显子 1 外，我们获得了 的极好覆盖（平均读深=88），包括重复和非重复区域。在 9 名具有典型 ADPKD 表现（双侧对称肾脏受累、阳性家族史、一致的影像学和肾功能）的患者中，4 名患者有蛋白截断 突变，1 名患者有 错义突变，1 名患者有 突变。这些变体以前在沙特人群中没有观察到。在 7 例临床诊断为 ADPKD 但特征不典型的病例中，未发现 或 突变，但在致囊候选基因中发现了罕见的预测致病性杂合变体，包括 、 和 。PKD1 和 PKD2 的突变是沙特具有典型 ADPKD 的 ADPKD 患者最常见的病因。ADPKD：常染色体显性遗传性多囊肾病；CFTR：囊性纤维化跨膜电导调节因子；EGF：表皮生长因子；MCIC：梅奥诊所成像分类；PKD：多囊肾病；TSC2：结节性硬化症复合物 2。
