Congenital nephrotic syndrome (NPHS1):: Features resulting from different mutations in Finnish patients
Congenital nephrotic syndrome (NPHS1):: Features resulting from different mutations in Finnish patients
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DOI：
10.1046/j.1523-1755.2000.00254.x
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发表时间：
2000-09-01
影响因子：
19.6
通讯作者：
Jalanko, H
中科院分区：
文献类型：
--
作者：
Patrakka, J;Kestilä, M;Jalanko, H
背景先天性肾病综合征（NPHS 1）是一种罕见的常染色体隐性遗传疾病。NPHS 1基因突变的NPHS 1儿童最近已被确定。该基因编码nephrin，一种足细胞的细胞表面蛋白。两种突变，名为Fin-major和Fin-minor，在90%以上的芬兰患者中发现。在这项研究中，我们将46名芬兰NPHS 1患儿的临床特征和肾脏表现与NPNS 1基因突变相关联。从患者档案中收集临床数据，并重新评价肾脏组织学和电子显微镜检查样本。采用免疫组化、Western blotting和原位杂交技术研究nephrin的表达。无论检测到的基因型如何，大多数患者在出生后几天内检测到肾病综合征。在不同突变的患者中，新生儿、肾脏、心脏或神经系统特征无差异。Nephrin在Fin-major或Fin-minor突变的肾脏中不表达，而另一种与Slit相关的蛋白。ZO-1，正常染色。电镜下可见足细胞融合和不同大小的足细胞滤过缝。然而，狭缝光阑不见了。与此相反，一名肾组织中表达nephrin的Fin-major/R743 C基因型肾病患儿，其裂孔隔膜正常，并对血管紧张素转换酶抑制剂和吲哚美辛治疗有反应。最常见的NPHS 1基因突变，鳍主要和鳍次要，都导致缺乏nephrin和足细胞狭缝隔膜，以及临床严重形式的NPHS 1。芬兰型先天性肾病综合征。
Background. Congenital nephrotic syndrome (NPHS1) is a rare disease inherited as an autosomally recessive trait. The NPHS1 gene mutated in NPHS1 children has recently been identified. The gene codes for nephrin, a cell-surface protein of podocytes. Two mutations, named Fin-major and Fin-minor, have been found in over 90% of the Finnish patients. In this study, we correlated the NPNS1 gene mutations to the clinical features and renal findings in 46 Finnish NPHS1 children.Methods. Clinical data were collected from patient files, and kidney histology and electron microscopy samples were re-evaluated. The expression of nephrin was studied using immunohistochemistry, Western blotting, and in situ hybridization.Results. Nephrotic syndrome was detected in most patients within days after birth regardless of the genotype detected. No difference could be found in neonatal, renal, cardiac, or neurological features in patients with different mutations. Nephrin was not expressed in kidneys with Fin-major or Fin-minor mutations, while another slit diaphragm-associated protein. ZO-1, stained normally. In electron microscopy, podocyte fusion and podocyte filtration slits of various sizes were detected. The slit diaphragms, however, were missing. In contrast to this, a nephrotic infant with Fin-major/R743C genotype expressed nephrin in kidney had normal slit diaphragms and responded to therapy with an angiotensin-converting enzyme inhibitor and indomethacin.Conclusions. The most common NPHS1 gene mutations, Fin-major and Fin-minor, both lead to an absence of nephrin and podocyte slit diaphragms, as well as a clinically severe form of NPHS1. the Finnish type of congenital nephrotic syndrome.