NPHS2 Variation in Focal and Segmental Glomerulosclerosis

Stephen J Tonna; Alexander Needham; Krishna Polu; Andrea Uscinski; Gerald B Appel; Ronald J Falk; Avi Katz; Salah Al-Waheeb; Bernard S Kaplan; George Jerums; Judy Savige; Jennifer Harmon; Kang Zhang; Gary C Curhan; Martin R Pollak


BMC Nephrology 

In This Article


Mutations in NPHS2 are a rare cause of FSGS of late onset. Most (but not all) individuals with adult onset FSGS attributable to NPHS2 mutations have one p.R229Q allele. Our findings are consistent with other recent reports.[9,10] We have demonstrated that NPHS2 mutations contribute to FSGS in 8% of the familial cases and 2.8% of the sporadic cases analyzed here. Furthermore, the most commonly found polymorphisms demonstrated in NPHS2 resequencing, p.R229Q and p.A242V, do not appear to cause FSGS, nor associate with proteinuria in the homozygous or heterozygous state. In addition, p.R229Q heterozygous events do not associate with measures of kidney dysfunction in diabetic individuals, and thus p.R229Q is unlikely to represent a major genetic modifier for proteinuria.