The role of chromatin-related epigenetic modulations in CAKUT

Congenital anomalies of the kidney and urinary tract (CAKUT) represent a major health burden in humans. Phenotypes range from renal hypoplasia or renal agenesis, cystic renal dysplasia, duplicated or horseshoe kidneys to obstruction of the ureteropelvic junction, megaureters, duplicated ureters, urethral valves or bladder malformations. Over the past decade, next-generation sequencing has identified numerous causative genes; however, the genetic basis of most cases remains unexplained. It is assumed that environmental factors have a significant impact on the phenotype, but, overall, the pathogenesis has remained poorly understood. Interestingly however, CAKUT is a common phenotypic feature in two human syndromes, Kabuki and Koolen-de Vries syndrome, caused by dysfunction of genes encoding for KMT2D and KANSL1, both members of protein complexes playing an important role in histone modifications. In this chapter, we discuss current knowledge regarding epigenetic modulation in renal development and a putatively under-recognized role of epigenetics in CAKUT.