NPHP3基因突变致婴幼儿期进展为终末期肾病的肾单位肾痨2例并文献复习

发布时间：2018-07-10 15:14

本文选题：婴儿期 + 幼儿期　；参考：《中国循证儿科杂志》2017年05期

【摘要】：目的总结2例在婴幼儿期进展为终末期肾病(ESRD)的NPHP3基因突变致肾单位肾痨(NPHP)患儿的临床特征及基因突变的特点。方法收集患儿的一般情况、肾活检、影像学、实验室检查和基因测序结果,并行文献复习。结果(1)2例均为男性,发病年龄3和17个月,均以黄疸、肝功能异常为首发症状,2例进展至ESRD的年龄分别为11和35个月。例1肾活检病理肾小管间质炎,肾小球轻度病变,未见囊肿;肝脏活检肝细胞弥漫性变性,间质纤维组织增生。未发现家族中有类似疾病。(2)行高通量测序结果显示,例1存在NPHP3基因C.2369AG(p.L790P)、c.1358AG(p.L453P)杂合错义突变,例2存在c.1174CT(p.R392X)无义突变和IVS26-3AG剪切突变。2例均为复合杂合突变,均分别来自患儿父母。p.L453P和p.L790P错义突变及IVS26-3AG剪切突变经软件预测为有害突变。除IVS26-3AG外均为新发现的突变。(3)共检索到18篇文献1 504例NPHP患者行NPHP3测序,79例检测到NPHP3纯合突变或复合杂合突变。其中19例在新生儿期进展为ESRD,需要肾脏替代治疗,常伴有肺发育不良和胰腺囊肿,在胎儿期表现为羊水少,超声提示双肾增大,伴有囊性改变,常被诊断为常染色体隐性遗传多囊肾;余20例(含文2例)在5岁前进展为ESRD,以肝功能异常和贫血为主要表现,常伴肝脏纤维化和胆管发育异常;42例在5岁后进展为ESRD,以贫血、肾功能异常和高血压等肾脏表型为主。结论 NPHP3基因突变所致NPHP并非传统意义上的青年型NPHP,约半数在5岁前进展为ESRD,故婴幼儿期不明原因的黄疸和肝功能异常应警惕NPHP3基因突变可能。本研究发现的c.1358AG、C.2369AG和c.1174CT突变为新发现的NPHP3基因突变类型。
[Abstract]:Objective to summarize the clinical characteristics and gene mutation of NPHP3 gene mutation in 2 infants with end-stage nephropathy (ESRD). Methods the general data of children, renal biopsy, imaging, laboratory examination and gene sequencing were collected and the literature was reviewed. Results (1) 2 cases were male, the age of onset was 3 months and 17 months. Jaundice and abnormal liver function were the first symptom. The age of ESRD was 11 and 35 months, respectively. Case 1 renal biopsy pathology renal tubulointerstitial inflammation, glomerular mild lesions, no cysts, liver biopsy liver cells diffuse degeneration, interstitial fibrous tissue proliferation. No similar diseases were found in the family. (2) the results of high-throughput sequencing showed that the heterozygous sense mutation of NPHP3 gene C.2369 AG (p. L790P) was found in case 1, and that in case 2 there was a compound heterozygous mutation in C. 1174CT (p. R392X) and in IVS26-3AG. The missense mutations and IVS26-3AG splicing mutations were predicted to be harmful mutations by software. All the mutations except IVS26-3AG were newly discovered. (3) A total of 18 references were found in 1 504 patients with NPHP, and 79 patients with NPHP3 were found to have homozygous or compound heterozygous mutations. 19 of them developed ESRD at the neonatal stage, requiring renal replacement therapy, often accompanied by pulmonary dysplasia and pancreatic cysts, and presented with oligohydramnios at the fetal stage. The remaining 20 cases (including 2 cases) developed ESRD before the age of 5 years, with liver dysfunction and anemia as the main manifestation, and 42 cases with hepatic fibrosis and abnormal bile duct development developed to ESRD after 5 years of age, the other 20 cases (including 2 cases) developed into ESRD after 5 years of age, and the other 20 cases (including 2 cases) were often diagnosed as autosomal recessive polycystic kidney. Renal dysfunction and hypertension were predominant in renal phenotypes. Conclusion NPHP3 gene mutation caused by NPHP is not a young NPHPin the traditional sense, and about half of the NPHP3 gene progresses to ESRD before the age of 5 years. Therefore, it is necessary to be alert to the mutation of NPHP3 gene in children with unknown causes of jaundice and abnormal liver function. The mutations of c. 1358 AGN C.2369 AG and c. 1174 CT were newly discovered mutations of NPHP3 gene.
【作者单位】：复旦大学附属儿科医院肾脏和风湿科;复旦大学附属儿科医院医学转化中心;
【分类号】：R726.9

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