Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations
Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations
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DOI：
10.1086/302182
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发表时间：
1999-01-01
影响因子：
9.8
通讯作者：
Tryggvason, K
中科院分区：
文献类型：
--
作者：
Lenkkeri, U;Männikkö, M;Tryggvason, K
芬兰类型（NPHS1）的先天性肾病综合征是一种常染色体隐性疾病，是由最近发现的肾素基因NPHS1（AF035835）突变引起的。该疾病属于芬兰疾病遗产，主要存在于芬兰，但在欧洲和北美地区有很多病例。肾素基因由29 kb的29个外显子组成，在19q13.1染色体区域。在本研究中，分析了肾素基因的基因组结构，并筛选了35例NPHS1患者的基因中存在突变。总共32个新型突变，包括缺失；插入；胡说八道，错过和剪接突变；发现了两个常见的多态性。只有两名瑞典和四名芬兰患者具有典型的芬兰突变：外显子2（FIN（MARIA））中的2 bp缺失或外显子26（FIN（FIR））中的无义突变。在七个情况下，在NPHS1基因的编码区域或直接5'Fanking区域中未发现突变。这些患者可能在启动子，内含子区域或编码另一种与肾素相互作用的蛋白质的基因中发生突变。
Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal recessive disorder that is caused by mutations in the recently discovered nephrin gene, NPHS1 (AF035835). The disease, which belongs to the Finnish disease heritage, exists predominantly in Finland, but many cases have been observed else:where in Europe and North America. The nephrin gene consists of 29 exons spanning 26 kb in the chromosomal region 19q13.1. In the present study, the genomic structure of the nephrin gene was analyzed, and 35 NPHS1 patients were screened for the presence of mutations in the gene. A total of 32 novel mutations, including deletions; insertions; nonsense, missense, and splicing mutations; and two common polymorphisms were found. Only two Swedish and four Finnish patients had the typical Finnish mutations: a 2-bp deletion in exon 2 (Fin(major)) or a nonsense mutation in exon 26 (Fin(minor)). In seven cases, no mutations were found in the coding region of the NPHS1 gene or in the immediate 5'-flanking region. These patients may have mutations elsewhere in the promoter, in intron areas, or in a gene encoding another protein that interacts with nephrin.