Woolf Adrian S, Stuart Helen M, Newman William G
Centre for Paediatrics Child Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK,
Pediatr Nephrol. 2014 Mar;29(3):353-60. doi: 10.1007/s00467-013-2472-1. Epub 2013 Apr 13.
Lower urinary tract and/or kidney malformations are collectively the most common cause of end-stage renal disease in children, and they are also likely to account for a major subset of young adults requiring renal replacement therapy. Advances have been made regarding the discovery of the genetic causes of human kidney malformations. Indeed, testing for mutations of key nephrogenesis genes is now feasible for patients seen in nephrology clinics. Unfortunately, less is known about defined genetic bases of human lower urinary tract anomalies. The focus of this review is the genetic bases of congenital structural and functional disorders of the urinary bladder. Three are highlighted. First, prune belly syndrome, where mutations of CHRM3, encoding an acetylcholine receptor, HNF1B, encoding a transcription factor, and ACTA2, encoding a cytoskeletal protein, have been reported. Second, the urofacial syndrome, where mutations of LRIG2 and HPSE2, encoding proteins localised in nerves invading the fetal bladder, have been defined. Finally, we review emerging evidence that bladder exstrophy may have genetic bases, including variants in the TP63 promoter. These genetic discoveries provide a new perspective on a group of otherwise poorly understood diseases.
下尿路和/或肾脏畸形是儿童终末期肾病最常见的共同病因，而且它们也很可能是需要肾脏替代治疗的年轻成年人中的一个主要亚组病因。在人类肾脏畸形的遗传病因发现方面已取得进展。的确，对于肾脏病门诊的患者而言，检测关键肾发生基因的突变现在是可行的。不幸的是，关于人类下尿路异常的明确遗传基础所知较少。本综述的重点是膀胱先天性结构和功能障碍的遗传基础。突出了三点。第一，梅干腹综合征，已报道编码乙酰胆碱受体的CHRM3、编码转录因子的HNF1B和编码细胞骨架蛋白的ACTA2发生了突变。第二，膀胱-面部综合征，已确定编码位于侵入胎儿膀胱的神经中的蛋白质的LRIG2和HPSE2发生了突变。最后，我们综述了新出现的证据，即膀胱外翻可能有遗传基础，包括TP63启动子中的变异。这些遗传学发现为一组原本了解甚少的疾病提供了新视角。
