Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, P.O.Box 85060, 3508 AB, Utrecht, The Netherlands.
Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, P.O.Box 85060, 3508 AB, Utrecht, The Netherlands.
Semin Cell Dev Biol. 2019 Jul;91:104-110. doi: 10.1016/j.semcdb.2018.08.013. Epub 2018 Sep 5.
Congenital abnormalities of the kidney and urinary tract (CAKUT) form the leading cause of pediatric end-stage renal disease. Knowledge on the molecular mechanisms that underlie CAKUT leads to the improvement of DNA diagnostics and counseling regarding prognosis and recurrence risk estimation for CAKUT patients and their relatives. Implementation of next generation sequencing in research and diagnostic settings has led to the identification of the molecular basis of many developmental diseases. In this review, we summarize the efforts on next generation sequencing in CAKUT research and we discuss how next generation sequencing added to our understanding of CAKUT genetics. Although next generation sequencing has certainly proven to be a game changer in the field of disease gene identification and novel CAKUT-causing gene variants have been identified, most CAKUT cases still remain unsolved. Occurring with genetic and phenotypic heterogeneity along with incomplete penetrance, the identification of CAKUT etiology poses many challenges. We see great potential for combined -omics approaches that include next generation sequencing in the identification of CAKUT-specific biomarkers, which is necessary to optimize the care for CAKUT patients.
先天性肾和尿路畸形（CAKUT）是小儿终末期肾病的主要原因。对 CAKUT 潜在分子机制的了解，有助于提高 DNA 诊断水平，并为 CAKUT 患者及其亲属提供预后和复发风险评估方面的咨询。下一代测序在研究和诊断环境中的应用，已经确定了许多发育性疾病的分子基础。在这篇综述中，我们总结了 CAKUT 研究中下一代测序的努力，并讨论了下一代测序如何帮助我们加深对 CAKUT 遗传学的理解。尽管下一代测序在疾病基因鉴定领域无疑是一个变革者，并且已经确定了许多新的 CAKUT 致病基因变异，但大多数 CAKUT 病例仍然未得到解决。CAKUT 的病因存在遗传和表型异质性以及不完全外显率等问题，这给鉴定带来了许多挑战。我们看到了将下一代测序与其他组学方法相结合，以鉴定 CAKUT 特异性生物标志物的巨大潜力，这对于优化 CAKUT 患者的护理是必要的。
