散发性肾病综合征患儿NPHS2基因突变及多态性

Mutation and polymorphism of NPHS2 gene in sporadic nephrotic syndrome children

目的研究散发性肾病综合征（NS）患儿NPHS2基因的突变和（或）多态性,为早期预测原发性NS患儿对常规激素治疗的反应性及预后提供帮助。方法聚合酶链反应法扩增基因组DNA,直接测序分析38例激素敏感型、22例激素抵抗型肾病综合征患儿NPHS2基因的突变和（或）多态性变化。结果发现3例患者携带NPHS2基因杂合错义突变（S206I、E188D）,1例患者携带一个新的无义突变（E237X）,导致蛋白质翻译的提前终止。发现两种NPHS2基因的多态现象（A318A、L346L）。结论中国散发性肾病综合征患儿存在NPHS2基因突变及多态性。NPHS2基因突变分析可能有助于早期预测这些患者对常规激素治疗的敏感性及预后。

Objective To study the mutation and polymorphism of podocin coding NPHS2 gene in sporadic primary nephrotic syndrome （NS） children in order to predict the responsiveness to regular steroid therapy and prognosis. Methods Genome DNA was amplified by PCR. Mutation and /or polymorphism of NPHS2 gene in 38 steroid-sensitive NS children, 22 steroid-resistant NS children and 30 healthy controls were examined by direct sequencing. Results Three patients were found to carry novel heterozygous allelic variants leading to amino acid substitution （S260I, E188D） and one to carry a novel nonsense mutation leading to a truncated protein product （E237X）. Two known polymorphisms were also found. Conclusions Mutation and polymorphism of NPHS2 gene are present in sporadic Chinese primary NS children. Genetic analysis may be beneficial to early predict the responsiveness to steroid and the prognosis of primary NS children.