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目的:检测不同病理类型散发性难治性肾病综合征(NS)患者NPHS2基因突变。方法:研究对象为1997年至2004年我院收治的19例散发性难治性NS患者,年龄4～48岁,男性15例,女性4例,其中激素不敏感患者7例,包括局灶节段性肾小球硬化(FSGS)5例,微小病变(MCD)1例,系膜增生性肾小球肾炎(MsPGN)1例;激素依赖患者12例,包括MCD6例,FSGS4例,未行肾穿刺2例。外周血基因组DNAPCR扩增后直接测序。间接免疫荧光法检测肾组织中podocin的表达。结果:①发现1例NPHS2基因431C>A的杂合突变,造成144位氨基酸由脯氨酸转变为组氨酸,查阅文献和基因库,未发现相同突变报道。该患者为激素依赖性NS,病理类型为FSGS。正常对照102条染色体中未发现同样突变。②发现11个SNP位点,其中3个位于外显子区,4个位于内含子区,1个位于启动子区,1个位于5’-UTR区,2个位于3’-UTR区。③该患者肾组织中podocin表达明显减弱。结论:在1例激素依赖NS患者中发现1个新的NPHS2基因突变,且肾组织中podocin蛋白表达明显减弱。推测该例患者发病和激素治疗反应差可能与NPHS2突变有关。
Objective: To detect NPHS2 gene mutations in patients with sporadic refractory nephrotic syndrome (NS) of different pathological types. Methods: Nineteen patients with sporadic refractory NS were enrolled in our hospital from 1997 to 2004, aged 4 to 48 years, 15 males and 4 females, including 7 hormone-insensitive patients, including focal section 5 cases of segmental glomerulosclerosis (FSGS), 1 case of minimal change (MCD) and 1 case of mesangial proliferative glomerulonephritis (MsPGN). There were 12 cases of hormone dependent patients including 6 cases of MCD, 4 cases of FSGS, Puncture in 2 cases. Peripheral blood genomic DNA was amplified directly by PCR. Indirect immunofluorescence detection of podocin expression in renal tissue. Results: ① A heterozygous mutation in 431C> A of NPHS2 gene was found, resulting in the change of amino acid 144 from proline to histidine. References and gene pools were not found. This patient is a hormone-dependent NS with a pathological type of FSGS. No mutation was found in the normal control 102 chromosomes. ② Eleven SNPs were found, of which three were located in the exon, four in the intron, one in the promoter region, one in the 5’-UTR region and two in the 3’-UTR region. ③ The expression of podocin in the kidney of the patients was obviously weakened. CONCLUSIONS: One new NPHS2 gene mutation was found in one patient with hormone-dependent NS and the expression of podocin protein in renal tissues was significantly decreased. Presumably the patients with poor response to the disease and hormone therapy may be related to NPHS2 mutations.