丁洁
以儿科学,儿科肾脏病学位主要研究方向
个性化签名
- 姓名:丁洁
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
儿科学
- 研究兴趣:以儿科学,儿科肾脏病学位主要研究方向
1982年毕业于北京医学院医疗系,1989年完成中美联合培养博士生项目并获北京医科大学医学博士学位,1994年在美完成博士后工作。现为北京大学第一医院副院长,儿科教授、研究员、博士生导师。现任国际小儿肾脏病学学会理事,亚洲小儿肾脏病学学会理事;任中华医学会儿科学分会中青年委员,中华医学会儿科学分会儿肾学组秘书,中华医学会医疗事故技术鉴定专家库成员,中国医师协会儿童健康专业委员会常务委员;北京大学学报(医学版),副主编,临床儿科杂志副主编,肾脏病与透析肾移植杂志常务编委,中华儿科杂志编委及英文摘要编审,以及中国实用儿科杂志、实用儿科临床杂志、中国当代儿科杂志编委会、小儿急救杂志等国内学术期刊编委,同时还应邀担任国际儿科肾脏病杂志(Pediatric Nephrology)、美国肾脏病杂志(American Journal of Kidney Diseases)、国际肾脏病杂志(Kidney International)的审稿专家。一直以儿科学,儿科肾脏病学位主要研究方向,从事小儿肾脏疾病的研究和临床工作,尤其儿童遗传性肾脏病诊断、相关致病基因分析及蛋白尿发生机制的研究。
作为课题负责人主持十余项国家级、部委级及北京市级科研课题;作为第一作者或责任作者在国际和国内学术期刊发表学术论文110余篇,应邀在国际学术会议演讲10余次、国内学术会议数十次。作为研究生导师培养研究生(含在读研究生)16位(硕士研究生5位,博士研究生11位)。作为第一完成人曾获得国家科学技术进步奖(二等,2005年)、中华医学科技奖(一等,2004年)、北京市科技进步奖(二等,2000年)各一次,多次获全国学术会议及中华医学会优秀论文奖。
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【期刊论文】糖皮质激素受体基因多态性与肾病综合征患儿激素耐药相关性探讨
丁洁, 叶建伟, 黄建萍, 陈彦, 姚勇, 肖慧捷, 杨霁云, 沈颖, 孟群
中华儿科杂志,2003,41(9):661-665,-0001,():
-1年11月30日
目的:筛选人类糖皮质激素受体基因(NR3C1)的多态性,并分析其在激素耐药型、激素敏感型肾病综合征患儿以及参照人群(随机抽取的脐血标本)中的分布,以研究NR3CI多态性与肾病综合征患儿激素耐药的关系。方法:提取39例激素耐药型、67例激素敏感型肾病综合征患儿以及64例参照人群血基因组DNA,PCR扩增NR3CI中编码人类糖皮质激素受体全都功能区的第2-9α外显子,以变性高效液相色谱(DHPLC)分析检测PCR产物,对洗脱曲线异常者进行DNA浏序。结果:在总计170份基因组DNA样本中,DHPLC分析发现12种多态性,均经DNA测序证实。另外,有3组多态性呈紧密连锁的单倍型([198G>A+200G>A],[1374A>G+IVSG-68-IVSG-63delAAAAAA +IvsH-9C>G +2382C>T],[1896C>T+2166c>T +2430T>C])。后2种单倍型为首次报道,它们在激素耐药型肾病综合征组的基因型频率(10.3%和15.4%)明显高于敏感型肾病综合征(1.5%和7.5%),2种单倍型的OR值分别为7.54和2.26。其余多态性在各组中出现频率相对较低。结论:在NR3CI基因中筛选出12处多态性;而且新发现的2种多位点紧密连锁的单倍型可能与肾病综合征患儿发生糖皮质激素耐药有关。
受体,, 糖皮质激素, 多态现象(, 遗传学), , 抗药性, 肾病综合征, 色谱法,, 高压液相
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【期刊论文】Alport syndrome with neurofibromatosis type-I: a case report
丁洁, Jie Ding, Ji-Yun Yang, Yong Yao, Jing-Cheng Liu, Yun-Bi Li, and Li-Xia Yu
Pediatr Nephrol (1997) 11: 649-650,-0001,():
-1年11月30日
We report a 9-year-old boy with repeated fractures of the tibia from age 6 months and microscopic hematuria from age 2 years. His maternal family has a history of nephritis and his paternal family has neurofibromatosis type-I (NF-I). The boy's renal biopsy revealed an irregular attenuation and splitting of the glomerular basement membrane. The skin biopsy was stained with monoclonal antibody against the a5 chain of type IV collagen; the epidermal basement membrane was negative in the boy and segmentally positive in the boy's mother. We conclude that the patient inherited Alport syndrome from his mother and NF-I from his father. We postulate this was a chance association and that this case does not suggest any relationship between the two diseases.
Alport syndrome-Neurofibromatosis type-I-Type IV collagen-Glomerular basement membrane-Epidermal basement membrane
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【期刊论文】A novel mutation of NPHS2identified in a Chinese family
丁洁, Zihua Yu
,-0001,():
-1年11月30日
Since the identification of the NPHS2 gene, which encodes podocin, several groups from European, Middle Eastern, and North American countries have reported NPHS2 mutations in families with steroid-resistant nephrotic syndrome (SRNS) or focal segmental glomerulosclerosis (FSGS). Families with SRNS have also been reported in China with a population of more than 1.3 billion. However, to our knowledge, there is no mutational analysis of the NPHS2 gene in familial SRNS or FSGS in China. We identified a novel mutation of NPHS-(467-468insT and 503G>A) in a Chinese family with autosomal recessive SRNS using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing techniques. The results demonstrate that there is also NPHS2 mutation in Chinese familial SRNS. Therefore, Chinese SRNS patients with a familial history of NS should also be screened for possible mutations of NPHS2. We also detected clearly decreased staining with a specific podocin C-terminal antibody (P35) and negative staining with a specific podocin Nterminal antibody (P21). These results were contrary to those predicted from the mutated sites. Further studies are needed to explore the mechanism and impact of the mutant gene on the expression and localization of the relevant protein.
Steroid-resistant nephrotic syndrome, NPHS2, Podocin, Focal segmental glomerulosclerosis, Chinese
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【期刊论文】Effect of the Knockdown of Podocin mRNA on Nephrin and α-Actinin in Mouse Podocyte
丁洁, QINGFENG FAN, JIE DING, , JINGJING ZHANG, NA GUAN, AND JIANGHONG DENG
Exp Biol Med 229: 964-970, 2004,-0001,():
-1年11月30日
Recently, the novel podocyte proteins podocin, nephrin, and aactinin-4 have been identified in three congenital/family nephritic syndromes, respectively. Further studies showed that these podocyte proteins were involved in some acquired nephrotic syndromes and various experimental models of proteinuria. However, the molecular interactions among these podocyte proteins remain unclear. In this study, to investigate the molecular interactions among podocin, nephrin, and aactinin-4, we reconstructed the RNA interference (RNAi) expression vector, pSilencer 2.1-U6, specifically targeting podocin mRNA, and it was transfected into the mouse podocyte clone (MPC5). Immunofluorescence staining, double-immunolabeling, confocal microscopy, semiquantitative reverse transcription polymerase chain reaction (RT-PCR), and Western blotting were used to detect the distribution and expression of podocin, nephrin, a-actinin-4, and glyseraldehyde-3-phosphate dehydrogenase (GAPDH)/b-actin. The fluorescence intensity of podocin and nephrin decreased obviously, along with the evident distribution change from the cell membrane surface to the nucleus circumference in podocyte. In relation to GAPDH, the mRNA reductions of podocin and nephrin were observed by about 65% and 70%, respectively. The expression of podocin protein was too low to be detected in the interference group. In relation to b-actin, the protein level of nephrin decreased by about 78%. The distribution and the mRNA and protein level of aactinin showed no appreciable change. Alpha-actinin localized mainly in the cytoplasm and also extended to the processes. Thus, the significant decreased expression of nephrin along with the redistribution were detected with the knockdown of podocin mRNA, whereas the expression and distribution of aactinin-4 showed no change. These results suggest that podocin may interact directly with nephrin, but not with aactinin.
RNA interference, podocyte, podocin, nephrin, alphaactinin
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【期刊论文】Mutations in NPHS2 in sporadic steroid-resistant nephrotic syndrome in Chinese children
丁洁, Zihua Yu, Jie Ding, Jianping Huang, Yong Yao, Huijie Xiao, Jingjing Zhang, Jingcheng Liu and Jiyun Yang
Nephrol Dial Transplant (2005) 20: 902-908,-0001,():
-1年11月30日
Background. Since the identification of the NPHS-gene, various investigators have demonstrated that an NPHS2 mutation is a frequent cause of sporadic steroid-resistant nephrotic syndrome (SRNS), and occurs in 10.5–28% of children with the syndrome. Idiopathic nephrotic syndrome (INS) is also the most frequent glomerular disease in Chinese children, of which 20% of cases show steroid resistance. To our knowledge, however, whether or not NPHS2 is the causative gene in Chinese sporadic SRNS has not been established. This study aims to examine mutations in NPHS2 in Chinese children with sporadic SRNS. Methods. We examined 23 Chinese children with sporadic SRNS for mutations in NPHS2. The mutational analysis of NPHS2 was performed by polymerase chain reaction, denaturing high-performance liquid chromatography and DNA sequencing. Results. A heterozygous missense mutation of L361P in exon 8 of NPHS2 was detected in one of 23 children with sporadic SRNS, whereas it was not found in 53 controls. We also identified seven NPHS2 polymorphisms, -51G>T, 288C>T, IVS3-46C>T, IVS3-21C>T, IVS7-74G>C, 954T>C and 1038A>G, in some patients and controls. There was no significant difference in the genotypic and allelic frequencies of these polymorphisms between the patients and controls. Conclusion. The results demonstrate that NPHS-mutations are also present in Chinese sporadic SRNS. Our investigation supports the necessity of searching for mutations in NPHS2 in Chinese children with sporadic SRNS.
Chinese, NPHS2, steroid-resistant nephrotic syndrome
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【期刊论文】Phenotypic and genotypic features of Alport syndrome in Chinese children
丁洁, Fang Wang
Pediatr Nephrol (2002) 17: 1013-1020,-0001,():
-1年11月30日
ction (PCR)-single-strand conformation polymorphism analysis or PCR direct sequencing in 30 of the 44 patients. The clinical data showed that all patients had hematuria; 25 of 29 male patients (86%) and 9 of 15 female patients (60%) had proteinuria; 11 of 29 male patients (38%) and 1 of 15 female patients (7%) had nephrotic-level proteinuria; 10 of 21 male patients examined (48%) and 1 of 12 female patients examined (8%) had hearing abnormalities. Renal function remained normal despite hearing abnormalities, and ocular lesions occurred in 10%. Among 30 of 44 patients who had a family history of end-stage renal disease (ESRD), 80% (24/30) belonged to X-linked juvenile kindreds, and 20% (6/30) patients to adult kindreds. Of the 44 patients, 14 did not have a family history of ESRD, while 11 of 14 patients diagnosed with X-linked AS did. DNA analysis revealed four missense mutations, two silent mutations, one substitution, and one in-frame deletion. PCR along with Southern hybridization analysis revealed a large deletion of the paired COL4A5 and COL4A6 genes. Chinese AS patients were characterized clinically with hematuria, heavy proteinuria, and more juvenile forms. Mutations in these patients were usually small mutations, while a large deletion involving the 5′part of both COL4A5 and COL4A6 genes was identified.
Alport syndrome, Hereditary nephritis, Clinical features, Type IV collagen genes, Mutation detection
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【期刊论文】X连锁型Alport综合征女性COIAA5基因型及表型分析
丁洁, 郭顺华, 俞礼霞, 张英, 扬霁云
中华儿科杂志,2001,39(7):390~393,-0001,():
-1年11月30日
目的:认识Alporl综合征(As)女性临床表型以及基因型特征。方法:As女性共9例,年龄2-62岁;临床表现以血尿为主,伴蛋白尿(+)-(++),除1例血BUN和肌酐升高,其余患者在进入本研究时肾功能均正常未发现典型的眼部病变及感音神经性耳聋。As男性共11例,年龄228岁;临床表现为血尿、蛋白尿(+)-(++++),2例进人本研究时(分别为17岁和28岁)已出现尿毒症或因尿毒症已行肾移植;7例伴有感音神经性耳聋,2例伴有限部病变。以正常皮肤组织对照4例、正常肾组织对照2例及健康成人6例基因组DNA为对照。应用间接免疫荧光学方法,检测8/9例AS女性和9/11例As男性皮肤基底膜、3/9例AS女性和6/11例As男性肾脏基底膜Ⅳ型胶原n 5链。应用PCR-SSeP方法分析全部研究对象的COL4A5基因全部51个外显子,出现多态性的外显子直接测序分析。结果:As女性与AS男性相比,临床症状相对轻,少有出现肾功能减退,多不伴有肾外症状。(1)AS女性皮肤和肾脏基底膜a5(Ⅳ)链均为同断阳性,而正常对照为连续用性、男性As表现为完全阴性。(2)PCR-SSCP分析显示5/9例女性AS患者分别在第4、9、20、39和第46外显子扩增产物的DNA条带出现特殊的迁移类型:DNA单链既有与正常对照的DNA迁移率相同的条带,同时还有不同于正常对照的DN-4.单链条带。(3)其中1例As女性第4外显子DNA序列分析显示两种序列,-种与正常序列相同,另-种DN_4.序列出现c-A碱基替代突变。结论:X连锁型女性As基因异常的特点为“杂台”,这种“杂台”状态可能成为女性As临床表型相对较轻的分子基础。
肾炎,, 遗传性, 基因型, 表型
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【期刊论文】伴食管平滑肌瘤的Alport综合征基因突变特征*
丁洁, 王芳, 俞礼霞, 杨霁云
肾脏病与透析移植杂志,2003,12(3):207~210,-0001,():
-1年11月30日
目的:认识我国伴食管平滑肌瘤的Alport综合征患者的基因型特点。方法:对1例中国汉族伴食管平滑肌瘤的Alport综合征男性患者应用PCR方法扩增COIAA5基因的外显子1、2和COIAA6基因的外显子1(部分序列)、2及3,同时应用Souem 杂交的方法进行DNA重组分析。结果:经PCR扩增和Souem杂交的方法揭示患者具有累及COL4A5和COIAA6两个基因5’端的大片段缺失,缺失范围可能至少包括COIAA5基因的外显子1、COIAA6基因的外显子1~2以及两基因间的启动子,估计此大片段缺失的断点在COIAA5基因的内含子1至COIAA6基因的内含子2中。结论:首次发现中国汉族中伴食管平滑肌瘤的Alport综合征患者具有COIAA5和COIAA6两个基因的缺失突变,该突变有可能累及COIAA6基因的内含子2。同时亦提示具有COIAA5和COIAA6两个基因突变伴弥漫性平滑肌瘤表型的Alport综合征患者与COIAA6基因突变位置有关。
Alport综合征, 弥漫性平滑肌瘤, Ⅳ型胶原, 基因突变
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丁洁, 柴青, 刘景城, 张英, 杨霁云
肾脏病与透析移植杂志,2000,9(2):123~125,-0001,():
-1年11月30日
摘要 目的:检测薄基底膜肾病(TBblN)患者基底膜中Ⅳ型胶原a链的表达,探讨其发病机制;并与Alp综合征(As)比较,为鉴别删和AS提供帮助。 方法:用抗Ⅳ型胶原不同n链的单克隆抗体,采用链菌素亲生物素一过氧化酶连接法检测了6例TBMN、3例x连锁型AS男性患儿及2例正常对照肾脏组织基底膜中Ⅳ型胶原al、、和 链的表达;采用间接免疫荧光法检测了3倒TBI~'、4例X链锁型AS男性患儿及4例正常对照皮肤基底膜中al(Ⅳ)和 (Ⅳ)链的表达。 结果:删患儿肾小球基底膜中1V型胶原n1、03—5链表达同正常.均为沿基底膜连续线状沉积。x连锁型AS男性患儿肾小球基底膜显示Ⅳ型胶原a1链染色阳性,而03~5链染色均为阻性。删、AS患儿及正常对照皮肤基底膜中al(1g)链染色均为沿基底膜连续线状沉积;而 (Ⅳ)链染色仅在AS为阴性,在TBMN和正常对照均为连续线状沉积。 结论:'I'BNN患儿基底膜中a(1g)链表达不同于AS。
薄基底膜肾病, Ⅳ型胶原, Alport综合征
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【期刊论文】检测不同组织基底膜IV型胶原a链确定Alport综合征遗传型
丁洁, 姚勇, 黄健萍, 郭顺华, 俞礼霞, 杨霁云
中华儿科杂志,1999,37(2):90~93,-0001,():
-1年11月30日
目的:探讨中国人不同遗传型Alport综舍征(As)患者基底膜a链的表达及其在判断遗传型方面的应用。方法应用间接免疫荧光学方法,对确诊为As的7例x连锁显性遗传型男性先证者、1例无家旗史的As女童及其部分家系成员不同组织基底膜中Ⅳ型胶原a链[a(Ⅳ)]的表达进行了检测井与正常组对照。结果X连锁显性遗传型男性患者,皮肤基底膜(EBM)~S(Ⅳ)链、肾小球基底膜(GBM)、肾小管基底膜(1BM)及肾小囊(BC)的03—05(IV)链均无表达;此类患者母亲的EBM上05(IV)链为间断性表达。无家族史的As女童,(Ⅳ)在EBM表达正常,但 (IV)链在GBM上无表达,在BC和部分"IBM上有表达:而 (Iv-)和 (IV)链在GBM、I"BM和BC上均无表达。这一表达特点符台国外报道的常染色体隐性遗传壅As患者基底膜n(Ⅳ)的表达。结论检测基底膜Ⅳ 型胺原a链的表达不但可诊断As患者和筛查基因携带者,而且可用于确定As遗传型,这对于小家系以及家旗史不确定的患者尤为重要。
肾炎,, 遗传性, 胶原, 肾小球膜
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