本文選題：嬰兒期 + 幼兒期��； 參考：《中國循證兒科雜志》2017年05期

【摘要】：目的總結(jié)2例在嬰幼兒期進(jìn)展為終末期腎病(ESRD)的NPHP3基因突變致腎單位腎癆(NPHP)患兒的臨床特征及基因突變的特點(diǎn)。方法收集患兒的一般情況、腎活檢、影像學(xué)、實(shí)驗(yàn)室檢查和基因測序結(jié)果,并行文獻(xiàn)復(fù)習(xí)。結(jié)果(1)2例均為男性,發(fā)病年齡3和17個(gè)月,均以黃疸、肝功能異常為首發(fā)癥狀,2例進(jìn)展至ESRD的年齡分別為11和35個(gè)月。例1腎活檢病理腎小管間質(zhì)炎,腎小球輕度病變,未見囊腫;肝臟活檢肝細(xì)胞彌漫性變性,間質(zhì)纖維組織增生。未發(fā)現(xiàn)家族中有類似疾病。(2)行高通量測序結(jié)果顯示,例1存在NPHP3基因C.2369AG(p.L790P)、c.1358AG(p.L453P)雜合錯(cuò)義突變,例2存在c.1174CT(p.R392X)無義突變和IVS26-3AG剪切突變。2例均為復(fù)合雜合突變,均分別來自患兒父母。p.L453P和p.L790P錯(cuò)義突變及IVS26-3AG剪切突變經(jīng)軟件預(yù)測為有害突變。除IVS26-3AG外均為新發(fā)現(xiàn)的突變。(3)共檢索到18篇文獻(xiàn)1 504例NPHP患者行NPHP3測序,79例檢測到NPHP3純合突變或復(fù)合雜合突變。其中19例在新生兒期進(jìn)展為ESRD,需要腎臟替代治療,常伴有肺發(fā)育不良和胰腺囊腫,在胎兒期表現(xiàn)為羊水少,超聲提示雙腎增大,伴有囊性改變,常被診斷為常染色體隱性遺傳多囊腎;余20例(含文2例)在5歲前進(jìn)展為ESRD,以肝功能異常和貧血為主要表現(xiàn),常伴肝臟纖維化和膽管發(fā)育異常;42例在5歲后進(jìn)展為ESRD,以貧血、腎功能異常和高血壓等腎臟表型為主。結(jié)論 NPHP3基因突變所致NPHP并非傳統(tǒng)意義上的青年型NPHP,約半數(shù)在5歲前進(jìn)展為ESRD,故嬰幼兒期不明原因的黃疸和肝功能異常應(yīng)警惕NPHP3基因突變可能。本研究發(fā)現(xiàn)的c.1358AG、C.2369AG和c.1174CT突變?yōu)樾掳l(fā)現(xiàn)的NPHP3基因突變類型。
[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.
【作者單位】： 復(fù)旦大學(xué)附屬兒科醫(yī)院腎臟和風(fēng)濕科;復(fù)旦大學(xué)附屬兒科醫(yī)院醫(yī)學(xué)轉(zhuǎn)化中心;
【分類號(hào)】：R726.9

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