Case Report And Gene Analysis Of A Patient With NPHS1 Gene Mutation-related Steroid?resistant Nephrotic Syndrome

Objectives To understand the clinical and pathological features of hereditary steroid?resistant nephrotic syndrome,and to improve the early diagnosis,differential diagnosis and treatment of the disease.Methods A patient with family history of renal disease of steroid?resistant nephrotic syndrome was selected as the study object,the clinical data of the patient and her immediate family was collected,and percutaneous renal biopsy was performed.NGS of genes relative with steroid?resistant nephrotic syndrome was applied to the patient and her parents,and Sanger sequencing was applied to conform the mutation been found.Results(1)A female girl patient,six years old,was admitted to the Affiliated Hospital of Qingdao University in July,2017 due to the notice of facial edema for two days,accompanied with decrease in urine volume for half a day.Urinalysis showed proteinuria of 4+,occult blood 2+,hematuria with urine red blood cells count of 61.90/ul,urine white blood cells count 89.00/ul,24-hour urine protein quantification 150mg/Kg,serum albumin 15.7g/L,serum urea nitrogen 14.64mmol/L,serum creatinine 65.6mmol/L,serum complement C3 0.76g/L,C4 0.12g/L,clinical diagnosis was nephritis nephrotic syndrome.Her father was diagnosed with steroid-resistant nephrotic syndrome in 2016,and the pathological type of renal puncture was membranous nephropathy.Other first and second degree relatives had no history of kidney disease.(2)The patient received adequate glucocorticoid(prednisone 2 mg/(kg.d))treatment for 4 weeks,and it showed no improvement.There was no ineffective after 3 courses of methylprednisolone pulse treatment.So it Conformed to steroid-resistant nephrotic syndrome.Immunosuppressant was added,and at the same time the glucocorticoids were reduced and discontinued at 12 months after onset.The following treatment with tacrolimus for 14 months and cyclosporine for 3 months,at the same time the patient was given telmisartan,benazepril hydrochloride,calcium,vitamin D preparation and Chinese medicine orally,it showed no effect.The urinalysis showed proteinuria of 3+ ～ 4+,kidney function was damaged gradually.She underwent hemodialysis 18 months after onset and is currently awaiting the kidney transplant.(3)Renal biopsy was applied,light microscopy showed that segmental mesangial proliferative of glomeruli,immunofluorescent Staining showed IgG:segmental +,IgA:-,IgM:-,C3:--C1q:-,κ chain:-,λ chain:-,and electron microscopy showed that diffuse foot process fusion of epithelial cells,without electron-dense deposit conform to the podocytopathies.(4)Gene sequencing showed the patient had three heterozygous mutations of c.803 G >A,c.1339G>A,and c.1802G> C in the NPHS1 gene.The mutation of c.803 G >a came from her father,and the mutations of c.1339G>A、c.1802G>C came from her mother.Conclusion 1.The clinical and routine assistive examinations of patient who with steroid-resistant nephrotic syndrome associated with mutations in the NPHS1 gene lack specificity.2.When the patient,s renal biopsy who with steroid-resistant nephrotic syndrome is non-minimal change disease,and immunofluorescence is negative,and electron microscopy shows no electron-dense deposit,We should routinely do genetic tests on the patient,and identify heritable steroid-resistant nephrotic syndrome at an early stage.3.Gene sequencing showed the patient had three heterozygous mutations of c.803 G >A,c.1339G>A,and c.1802G> C in the NPHS1 gene.The three heterozygous mutations all have pathogenicity.It is the autosomal recessive inheritance.And the mutation of c.803G>A was found for the first time.