CAJ | 학술논문

目的探讨Denys-Drash综合征(DDS)的临床病理特征,以加深对DDS的认识.方法总结2009至2011年诊治3例DDS患儿的临床病理特点和WT1检测结果,并结合文献复习.结果 3例DDS,例1、例2为核型46 XX、外生殖器正常女性,例3为男性伴双侧腹股沟隐睾.肾病起病年龄分别为1岁9个月、2岁4个月及3个月.例2、例3激素治疗无效.例1使用他克莫司,血浆白蛋白、胆固醇有改善,尿蛋白无缓解.例2用环孢素A、他克莫司蛋白尿均能缓解;现4岁9个月,蛋白尿缓解,肾功能正常.3例均是右肾单侧Wilms瘤,残肾病理均为弥漫系膜硬化.WT1检测:例1为外显子9的c.1213 C＞G错义突变,为新突变;例2、例3分别为c.1168 C ＞T无义突变和c.1130 A＞T错义突变.结论 DDS肾病临床表现变化较大,起病多较早,肾衰竭常在4岁以前出现,少数起病及肾衰竭出现较晚.其蛋白尿对激素治疗无效,但对钙神经素抑制剂环孢素A有效;本研究2例患儿使用他克莫司亦有效.DDS多因WT1突变所致,肾脏病理主要为弥漫系膜硬化.
목적 탐토Denys-Drash종합정(DDS)적림상병리특정,이가심대DDS적인식.방법 총결2009지2011년진치3례DDS환인적림상병리특점화WT1검측결과,병결합문헌복습.결과 3례DDS,례1、례2위핵형46 XX、외생식기정상녀성,례3위남성반쌍측복고구은고.신병기병년령분별위1세9개월、2세4개월급3개월.례2、례3격소치료무효.례1사용타극막사,혈장백단백、담고순유개선,뇨단백무완해.례2용배포소A、타극막사단백뇨균능완해;현4세9개월,단백뇨완해,신공능정상.3례균시우신단측Wilms류,잔신병리균위미만계막경화.WT1검측:례1위외현자9적c.1213 C＞G착의돌변,위신돌변;례2、례3분별위c.1168 C ＞T무의돌변화c.1130 A＞T착의돌변.결론 DDS신병림상표현변화교대,기병다교조,신쇠갈상재4세이전출현,소수기병급신쇠갈출현교만.기단백뇨대격소치료무효,단대개신경소억제제배포소A유효;본연구2례환인사용타극막사역유효.DDS다인WT1돌변소치,신장병리주요위미만계막경화.
Objective To study the clinical and pathological features of Denys-Drash syndrome (DDS).Method Three DDS cases who were treated in our department from December 2009 to June 2011 were subjected to this study by reviewing of literature.Result Both case 1 and case 2 were female,with karyotype 46,XX.Case 3 was male with bilateral cryptorchidism.The ages of nephropathy onset of the three cases were 1 year and 9 months,2 years and 8 moths,and 3 months respectively.Proteinuria in case 2 and case 3 were evidenced to be resistant to steroid.Case 1 was partially responsive to tacrolimus,plasma albumin and cholesterol were improved,although proteinuria was persistent after Tacrolimus was administered.Remission was achieved in case 2 after administration of cyclosporine A and later tacrolimus,and her renal function remains normal till present (4 years and 9 months).Residue renal histology revealed diffused mesangial sclerosis (DMS) in all three patients.All of the three patients had developed right unilateral Wilms tumor.A novel WT1 missense mutation exon 9 c.1213C ＞ G was detected in case 1.WT1 exon 9 c.1168C ＞ T nonsense mutation and exon 8 c.1130A ＞ T missense mutation were detected in case 2 and case 3,respectively.Conclusion The clinical manifestation of nephropathy in DDS is variable.The majority present with early onset nephropathy and reach renal failure before the age of 4 years.But in a few patients,nephropathy can also be present much later and progress slowly.Proteinuria in DDS is resistant to steroid but is responsive to calcineurin inhibitors,including Cyclosporine A.The effectiveness of tacrolimus was also observed in this study.DDS is evidently caused by WT1 mutation.DMS is the characteristic renal pathological change in DDS.