Abstract: Objective · To screen NPHS2 mutations in adult focal segmental glomerulosclerosis(FSGS) patients based on a large Chinese FSGS cohort.  Methods · All patients were biopsy determined FSGS by the Department of Nephrology at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine. FSGS secondary to systemic disease and other hereditary kidney disease were excluded. After extraction of genomic DNA of peripheral blood, NPHS2 was screened by directly sequencing the exon/intron junction or high-throughput sequencing, including whole exon sequencing and Panel sequencing, and then verified by Sanger sequencing. One hundred  healthy controls were enrolled to validate candidate mutations.  Results · Two hundred and four FSGS patients were enrolled，including 52 familial(25.5%) and 152 sporadic patients(74.5%)，of which steroid-resistant FSGS patients accounted for 30.3%(46/152). By sequencing NPHS2 in all patients of the cohort (Sanger sequencing in 61 patients and high-throughput sequencing in 143 patients), 2 novel conserved mutations were identified, one homozygous mutation in sporadic steroid-resistant FSGS, p.N199I and one heterozygous mutation in familial FSGS, p.L321fx346. Both of them were not detected in 100 healthy controls. These two variants were predicted to be damaging by Polyphen, SIFT and Mutation Taster. Totally, the mutation rate of NPHS2 in the FSGS cohort was 1%.  Conclusion · Since the overall frequency of NPHS2 mutations is considerably low in Chinese adult-onset FSGS, NPHS2 is not the main disease-causing gene of this group of people.

Key words: focal segmental glomerulosclerosis, NPHS2, mutation screening