Many cellular structures directly imply specific biological functions. For example, normal slit diaphragm structures that extend from podocyte foot processes ensure the filtering function of renal glomeruli. These slits are covered by a number of surface proteins, such as nephrin, podocin, podocalyxin and CD2AP. Here we report a human patient presenting with congenital nephrotic syndrome, omphalocele and microcoria due to two loss-of-function mutations in PODXL, which encodes podocalyxin, inherited from each parent. This set of symptoms strikingly mimics previously reported mouse Podxl−/− embryos, emphasizing the essential function of PODXL in mammalian kidney development and highlighting this patient as a human PODXL-null model. The results underscore the utility of current genomics approaches to provide insights into the genetic mechanisms of human disease traits through molecular diagnosis. Mutations in an identified gene cause a previously unknown form of an infant kidney disease called congenital nephrotic syndrome (CNS). Researchers in South Korea and Canada, led by Hae Il Cheong and Murim Choi at Seoul National University, studied the genetic make-up of a new-born baby with CNS. They identified two different mutations, one inherited from each parent, in a gene coding for a protein called podocalyxin, which is present in the membrane of kidney cells called podocytes. The podocytes play a key role in building the blood-filtering structures of kidneys. This previously unknown type of CNS adds another layer of complexity to the varied causes of the condition. The researchers suggest that it also offers a good example of the usefulness of modern genetic analysis in identifying the causes of disease.