Whole-genome sequencing for CAKUT in an island population

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) are a broad spectrum of structural malformations of varying severity and renal outcome.1 They occur in 3-6 per 1,000 live births either as an isolated characteristic, in combination or as part of a multi-organ malformation syndrome. Dialysis and kidney transplantation have been life-saving to patients with the most severe forms of CAKUT. However, the disease burden is high. In recent years, several studies have been undertaken with the aim to uncover the underlying cause of the disease. Familial cases2 and mouse models3 of CAKUT suggest that genetics plays an important role in the development of renal malformations. A number of genes have been implicated with various modes of inheritance, but in most patients the disease-causing mutation remains to be discovered. Here, we report on our progress in elucidating the genetics of CAKUT in cases of Maltese origin using whole-genome sequencing (WGS) in 10 unrelated patients.