NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome
NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome
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DOI：
10.1038/74166
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发表时间：
2000-04-01
期刊：
影响因子：
30.8
通讯作者：
Antignac, C
中科院分区：
文献类型：
--
作者：
Boute, N;Gribouval, O;Antignac, C
家族性特发性肾病综合征代表了一组异质性肾脏疾病，包括常染色体隐性遗传类固醇耐药肾病综合征，其特征为儿童早期蛋白尿发作，快速进展为终末期肾病和局灶节段性肾小球硬化。一个致病基因，NPHS 2，定位于1 q25 -31，我们在这里报告其鉴定的定位克隆。NPHS 2几乎只在胎儿和成熟肾小球的足细胞中表达，并编码一种新的整合膜蛋白，podocin，属于stomatin蛋白家族。我们发现了十种不同的NPHS 2突变，包括无义突变、移码突变和错义突变，与疾病分离，这表明podocin在肾小球过滤屏障功能中发挥着至关重要的作用。
Familial idiopathic nephrotic syndromes represent a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. A causative gene for this disease, NPHS2, was mapped to 1q25-31 and we report here its identification by positional cloning. NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier.