新生儿先天性肾病综合征1例报道并文献复习

A case of neonatal congenital nephrotic syndrome and literature review

目的总结1例先天性肾病综合征WT1基因杂合突变患儿的临床资料,以提高对该病的认识。方法选取2016年7月22日中国人民解放军陆军第七十四集团军医院儿科收治1例先天性肾病综合征患儿,检测其尿常规和血生化指标。应用二代测序,对遗传病相关的436个基因外显子区进行直接测序,分析先天性肾病综合征相关基因,并利用同样方法检测先证者父母外显子基因突变状态。结果患儿尿常规检测显示大量蛋白尿,尿蛋白(+++),尿潜血(+++),血生化检测显示低蛋白血症、高胆固醇血症,间断给予白蛋白以及维持水电解质平衡治疗,因患儿病情逐渐加重,家长放弃治疗,办理出院。该先证者外显子基因分析显示:WT1基因(NM024426.4) Exon8:c.1301G>A;p.(Arg43His)杂合,可疑致病突变,为新发突变。应用同样方法,对该先证者父母突变位点WT1(NM024426.4)基因c.1301进行检测,均未检测到特定位点的基因突变,结合先证者父母基因测序结果,不能排除先证者携带嵌合型突变可能。结论 WT1基因的(NM024426.4)Exon8:c.1301G>A;p.(Arg43His)杂合突变是引起新生儿先天性肾病综合征的原因。对既往有死胎、死产以及不良孕史的孕妇,应在产前基因诊断采用孕20周羊水细胞基因组DNA检测胎儿突变情况,以避免类似疾病发生。

Objective Improving the understanding of the disease of congenital nephrotic syndrome with WT1 gene heterozygous mutation by summarizing one clinical case of the newborn. Method A case of congenital nephrotic syndrome admitted to the Department of Pediatrics of our hospital was selected. Using second-generation sequencing to sequence the exons of 436 genes related to genetic diseases directly and analyzing the genes related to congenital nephrotic syndrome. Result Routine urine test showed a large amount of proteinuria, urine protein(+++), urine occultation blood(+++), blood biochemical test showed hypoproteinemia and hypercholesterolemia.Intermittent treatment was given to albumin and water and electricity balance. Due to the gradual aggravation of the child’s illness, the parents gave up treatment and discharged the patient.Exon gene analysis of the proband showed that WT1(NM024426.4) Exon8: c.1301 g >a;p.(Arg43 His) heterozygosity was suspected to be a new pathogenic mutation. Using the same method, the parents of the proband tested the same mutation site WT1(NM024426.4)c.1301 and no such mutation was observed. Conclusion The WT1 gene(NM024426.4) Exon8: c.1301 G >a;p.(Arg43 His) heterozygous mutation might be the cause of neonatal congenital nephrotic syndrome. For pregnant women with previous history of stillbirth,and other adverse pregnancy, prenatal genetic diagnosis should be conducted to detect fetal mutations in amniotic fluid cell genomic DNA at 20 weeks’ gestation to avoid similar diseases.