NPHS1 Gene Mutations in Children with FSGS

Introduction: Among patients with nephrotic syndrome( NS ) in childhood, 80% patients are sensitive to steroids and have histological featured of minimal change NS. 10% to 20% of children with idiopathic NS are resistant to steroid, namely, steroid-resistant nephrotic syndrome (SRNS). About 60% of patients having SRNS with childhood onset usually have focal segmental glomerulosclerosis (FSGS) and its renal histologic features. FSGS is a serious chronic progressive glomerular disease in children. FSGS is main reasons for end stage kidney disease (ESKD) with childhood onset NS. More than 20 gene mutations have been found to cause the SRNS, and the mainly FSGS. Among them, NPHS1, NPHS2, WT1 and LAMB2 are common pathogenic genes for SRNS or FSGS in children. Case Description: The patient, 10 years old girl, was admitted to our hospital on May 1, 2024 with the diagnosis of nephrotic syndrome due to a continuously progressing facial edema 2 days ago ,and low urine output for half day. The kidney biopsy was done with the result of FSGS. The eGFR was 40 ml/min. Prednisolone was given as 2 mg/kg/day for 4 weeks. Since urinary protein could not be relieved, The child was treated with cyclophophamide. The whole exon sequencing (WES) was performed revealed a NPHS1 missense mutation c.1339G>A and c.1802G>C in the child, carried by her fatherr. e.1339G>A (p.Gly601Ala) has been reported to be associated with congenital nephrotic syndrome, Finnish type, and c.1802G>C (p.Glu447Lys) has been reported to be associated with steroid-resistant nephrotic syndrome. The c.1339G>A, c.1802G>C, which were predicted by Mutationtaster software as harmful mutations. The proteinuria persisted and the kindey function downhill quickly. She received CAPD since Feb. 6, 2025. Discussion: NPHS1 mutation can cause nephrotic syndrome with FSGS. The NPHS1 missense mutation c.1339G>A and c.1802G>C may be pathogenic in the child, and can lead to ESKD. The kidney biopsy should be performed as soon as there is clinical manifestation of SRNS to clarify the pathological type. Once the diagnosis of FSGS is confirmed, gene detection should be carried out as soon as possible.