首次发现1例局灶性节段性肾小球硬化症患儿PAX2基因新的移码变异及文献复习

A new frameshift variation of PAX2 gene in a child with focal segmental glomerulosclerosis and literature review

目的了解儿童遗传性慢性肾脏病的临床与病理特点,寻找其致病基因突变位点并分析基因突变与临床表型的关系,以期早期诊断,早期预防。方法收集徐州医科大学附属徐州儿童医院1例疑似为遗传性因素所致慢性肾脏病患儿及其直系亲属的临床资料,并行肾穿刺病理检查,同时采用二代基因测序方法对该患儿、患儿父母及妹妹进行基因检测,寻找可能的突变位点,并与该家系中正常个体进行比较。结果患儿为14岁男孩,3岁时起病,主要临床表现为蛋白尿、夜尿增多,未正规治疗。期间多次尿蛋白++~+++,且逐渐出现尿床症状,家长一直未予重视。2年前于当地医院查肝、肾功能,家长诉未见异常,2019年8月19日因尿床至我院就诊,门诊查尿蛋白+++,血尿素氮13.54 mmol/L,肌酐188μmol/L,肾脏超声提示双肾缩小,肾穿刺活检病理结果为局灶性节段性肾小球硬化症(FSGS)。基因检测示患儿PAX2基因存在c.143delGp.Gly48Valfs*35剪切位点突变,且目前尚未有人群携带记录,因而考虑该患儿为PAX2基因出现新的移码突变。结论该例患儿临床表现为慢性肾脏病,肾活检确诊为FSGS,基因检测PAX2基因发生新的移码变异。对于病因不明的慢性肾脏病患儿应注意完善肾脏病理及基因检测,有助于明确诊断。

Objective To understand the clinical and pathological characteristics of hereditary chronic kidney disease in children and explore the pathogenic gene mutation sites and the relationship between gene mutation and clinical phenotype,in order to achieve early diagnosis and early prevention.Methods A child patient with suspected hereditary chronic kidney disease who were admitted to Xuzhou Children′s Hospital Affiliated to Xuzhou Medical University were enrolled.Clinical data were collected from the patient and his immediate family members.Renal puncture biopsy was performed.Meanwhile,the second-generation gene sequencing was used to detect gene mutation sites in the patient,his parents and sister,and to identify possible mutation sites.These data were also compared with normal individuals in the family.Results The child patient was a 14-year old boy,who first presented symptoms at 3-year old,with the main clinical manifestations of proteinuria and nocturia,and did not receive normal treatment.Urine proteinuria(PRO)++-+++,with increasing bedwetting symptoms,which however did not attract much attention from his parents.Two years ago,hepatic and renal functions were examined in local hospitals,and no abnormalities were reported.On August 19,2019,the patient was admitted to our hospital for bedwetting,and the outpatient test showed urine PRO+++,blood urea nitrogen(BUN)13.54 mmol/L and creatinine(SCr)188μmol/L.Kidney ultrasound indicated shrunken kidneys in both sides.The pathological results of renal biopsy showed focal segmental glomerulosclerosis(FSGS).Gene sequencing indicated a PAX2 gene mutation at the c.143delGp.Gly48Valfs*35 cleavage site,and there is currently no record in the population.Therefore,it was considered that the patient had a new frameshift mutation in PAX2 gene.As there was no PAX2 gene mutation in his parents and sister,it was suggested that the PAX2 gene mutation was a de novo mutation.Conclusions The patient manifests with chronic kidney disease and diagnosed by renal biopsy with FSGS,with a new frameshift mutation of PAX2 gene through gene sequencing.For child patients with chronic kidney disease of unknown etiology,it is necessary to improve pathological examination in the kidneys and gene sequencing,in order to make a clear diagnosis.