NPHS1基因突变致儿童局灶性节段性肾小球硬化1例报告并文献复习

NPHS1 Gene Mutations in Children with Focal Segmental Glomerulosclerosis and Literature Review

摘要: 目的：通过总结1例局灶性节段性肾小球硬化症(FSGS)患儿NPHS1基因突变的临床资料，提高对NPHS1突变表型的认识，探讨NPHS1基因突变与FSGS的关系。方法：收集1例FSGS患儿的病史、实验室检查及家族史。应用外显子检测(NGS)对儿童及其父母进行全外显子高通量测序。同时进行生物信息学分析。采用双脱氧链末端合成终止法测序对高通量测序结果进行验证，并进行相关文献复习。结果：患儿，女，7岁，6岁起病，确诊为肾病综合征，应用糖皮质激素尿蛋白一直未转阴，肾脏穿刺病理结果提示FSGS。家族史，患儿父亲患有肾病综合征，病理诊断为膜性肾病。测序结果NPHS1基因有c.803G > A错义突变(由父亲携带)，和c.1339G > A、c.1802G > C错义突变(由母亲携带)。Mutationtaster软件预测的c.1339G > A、c.1802G > C为有害突变，c.803G > A突变存在多态性。c.1339G > A和c.1802G > C是NPHS1上由母亲携带的致病性突变，而c.803G > A突变目前未见报道。结论：NPHS1突变可引起儿童FSGS。突变c.803G > A可能是亚洲儿童新发突变，此突变进一步丰富了NPHS1基因谱。

Abstract: Objective: To summarize the clinical data of NPHSI gene mutation in a case of a child with focal seg-mental glomerulosclerosis (FSGS), to improve the understanding of NPHS1 mutation phenotype, to study the relationship between NPHSI gene mutation and FSGS. Method: Medical history, laboratory examination results and family history of a child with FSGS were collected. Exon detection (NGS) was applied to perform a full-exon high-throughout sequencing on the child and her parents. Mean-while, bioinformatics analysis was carried out. Sanger sequencing was used to verify the results of high-throughout sequencing, and relevant literature review was conducted. Result: The proband: female, 7 years old, onset on her age of six, developed nephrotic syndrome; result did not turn to be negative when Glucocorticoid uroprotein was applied; renal pathology indicated FSGS. Family sur-vey revealed that the father suffered nephrotic syndrome with a pathological diagnosis of mem-branous nephropathy. Sequencing found that the missense mutations of NPHS1 gene c.803G > A (carried by her father), c.1339G > A and c.1802G > C (carried by her mother) were found in child. The c.1339G > A, c.1802G > C, which were predicted by Mutationtaster software as harmful muta-tions, and c.803G > A mutation had polymorphism. The c.1339G > A and c.1802G > C, which have to be proven as a pathogenic mutationamutation carried by mother on NPHS1, while c.803G > A have not been reported at present. Conclusion: NPHS1 mutation can cause nephrotic syndrome with FSGS in children. Mutation c.803G > A is probably the newly discovered and further enriches the NPHS1 gene spectrum.