CH Wang, JH Mao, XL Ma, LP Shi

Abstract

Background: NPHS1 mutation is one of the major causes of congenital nephrotic syndrome (CNS). Studies have confirmed that approximately one-half of CNS cases are caused by recessive mutations in NPHS1. In China, there have been a few reports of NPHS1 mutation in infants with CNS which indicates NPHS1 may be the causative gene in sporadic Chinese CNS. In this study, NPHS1 mutations in a Chinese family with CNS were detected and analysed. Methods: A five-day-old male infant suffered generalised oedema, proteinuria, hypoproteinaemia, and hypoalbuminaemia. His kidney histology showed characteristics of CNS. Mutation analysis was made of all exons and exon/intron boundaries of NPHS1 in the infant and his parents using polymerase chain reaction and direct DNA sequencing. Results: Two compound heterozygous mutations, including 1019C>T (P340L) in exon 9 and 3478C>T (R1160Stop) in exon 27, were identified in the infant with CNS. Only 1019C>T (P340L) was identified in mother and 3478C>T (R1160Stop) in father respectively. Conclusions: These findings reconfirm that NPHS1 gene mutations also present in sporadic Chinese CNS cases. Genetic studies of NPHS1 gene should be performed in young infant with CNS for genetic counselling.

背景：NPHS1突變是先天性腎病綜合徵（CNS）的一個主要原因。研究已證實約半數CNS病例是由於NPHS1隱性突變導致。在中國，已有一些CNS患兒報告有NPHS1突變，這意味著中國嬰兒CNS零散的病例中NPHS1可能是一個致病基因。本研究中，一CNS中國家庭接受了NPHS1基因突變檢測，我們對其結果也進行了分析。方法：一名5天大嬰兒患有全身性水腫、蛋白尿、低蛋白血症及低白蛋白血症。其腎組織學檢查顯示有先天性腎病綜合徵CNS的特徵表現。我們對該患兒NPHS1的所有外顯子以及鄰近的外顯子／內含子進行基因突變分析，也對其父母進行了多聚酶鏈式反應檢測（PCR）及直接DNA測序。結果：在該患兒上發現兩混合雜合子突變，為外顯子9上的1019C>T（P340L）以及外顯子27上的3478C>T（R1160Stop）。而其母親僅出現外顯子9上的1019C>T（P340L）突變，而父親僅出現外顯子27上的3478C>T（R1160Stop）突變。結論：這些發現證實了NPHS1基因突變同樣表現在中國零散的CNS病例中。在對中國CNS新生患兒進行基因諮詢時，應同時進行NPHS1基因分析。