Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel.
Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel.
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DOI：
10.1136/jmedgenet-2015-103469
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发表时间：
2016-05
影响因子：
4
通讯作者：
Albaqumi M
中科院分区：
文献类型：
--
作者：
Al-Hamed MH;Kurdi W;Alsahan N;Alabdullah Z;Abudraz R;Tulbah M;Alnemer M;Khan R;Al-Jurayb H;Alahmed A;Tahir AI;Khalil D;Edwards N;Al Abdulaziz B;Binhumaid FS;Majid S;Faquih T;El-Kalioby M;Abouelhoda M;Altassan N;Monies D;Meyer B;Sayer JA;Albaqumi M
遗传性囊性肾病是终末期肾病的常见原因。超过50个纤毛病基因，其编码影响初级纤毛的结构和功能的蛋白质，与囊性肾病有关。为了确定胎儿和新生儿囊性肾病的表型和基因型，我们使用肾脏基因组，将产前超声检查和产后肾脏超声检查与靶向外显子测序相关联。对一组由44个家庭组成的队列进行了调查，其中受影响病例的产前肾脏超声扫描结果包括双侧囊性肾病、回声肾或肾脏增大。在该队列中，疾病表型严重，有36例死产或围产期死亡。肾外畸形，包括脑膨出，多指畸形和心脏畸形，符合纤毛病变表型，经常检测到。肾脏基因组检测确定了34个家庭中的21个（62%）的致病突变，其中患者和父母的DNA是可用的。在剩下的10个只有亲本DNA的家庭中，发现了7个推断的致病突变。总共在12个不同的基因中发现了突变，总共有13个新的致病变体，包括NEK 8中的推断的新变体。CC2D2A突变是我们队列中产前囊性肾病和疑似纤毛病变的最常见原因。在具有纤毛病变表型的家族中，使用靶向肾脏基因面板进行突变分析可以进行快速分子诊断，并为患者，父母及其医生提供重要信息。
Inherited cystic kidney disorders are a common cause of end-stage renal disease. Over 50 ciliopathy genes, which encode proteins that influence the structure and function of the primary cilia, are implicated in cystic kidney disease. To define the phenotype and genotype of cystic kidney disease in fetuses and neonates, we correlated antenatal ultrasound examination and postnatal renal ultrasound examination with targeted exon sequencing, using a renal gene panel. A cohort of 44 families in whom antenatal renal ultrasound scanning findings in affected cases included bilateral cystic kidney disease, echogenic kidneys or enlarged kidneys was investigated. In this cohort, disease phenotypes were severe with 36 cases of stillbirth or perinatal death. Extra renal malformations, including encephalocele, polydactyly and heart malformations, consistent with ciliopathy phenotypes, were frequently detected. Renal gene panel testing identified causative mutations in 21 out of 34 families (62%), where patient and parental DNA was available. In the remaining 10 families, where only parental DNA was available, 7 inferred causative mutations were found. Together, mutations were found in 12 different genes with a total of 13 novel pathogenic variants, including an inferred novel variant in NEK8. Mutations in CC2D2A were the most common cause of an antenatal cystic kidney disease and a suspected ciliopathy in our cohort. In families with ciliopathy phenotypes, mutational analysis using a targeted renal gene panel allows a rapid molecular diagnosis and provides important information for patients, parents and their physicians.