Nephrotic Syndrome With Mutations in NPHS2: The Role of R229Q and Implications for Genetic Counseling

Publication date: Available online 18 September 2018Source: American Journal of Kidney DiseasesAuthor(s): Ilse M. Rood, Jeroen K.J. Deegens, Dorien Lugtenberg, Ernie M.H.F. Bongers, Jack F.M. WetzelsMutations in the NPHS2 gene, which encodes the podocyte slit diaphragm protein podocin, cause autosomal recessive steroid-resistant nephrotic syndrome (Online Mendelian Inheritance in Man [OMIM] #600995). Basic research and clinical studies have provided important insights about genotype-phenotype correlations. This knowledge allows personalized genetic (risk) counseling and should lead to changes in the advice given to patients. A patient who carries the R229Q variant (which has a high allele frequency of 3.7% in the European population) in combination with a pathogenic variant in exon 7 or 8 is at high risk for developing nephrotic syndrome that may not manifest before adulthood, whereas a patient with 2 pathogenic variants will develop congenital or childhood-onset nephrotic syndrome. In contrast, a patient who carries the R229Q variant in combination with a pathogenic variant in exons 1 to 6 is unlikely to develop nephrotic syndrome. In this article, we review the emerging knowledge about the NPHS2 gene and translate these findings from the bench to practical advice for the clinical bedside.
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research