摘要：目的 了解我国X伴性显性(XD)遗传Alport综合征(AS)中COL4A5基因突变特点。方法应用聚合酶链反应(PCR)-变性梯度凝胶电泳(DGGE)和直接测序的方法，对来自7个XD-AS家系10个成员和100个正常人外周血DNA标本进行了COL4A5基因43号外显子的检测。结果在一个家系中发现4142C→T(Pro1314Ser)的转换突变，先证者与其弟、其母均发现有此异常。结论 表明该突变为一遗传性突变。查阅基因库，未发现相同突变报道。

A novel COL4A5 gene mutation detected in one Alport syndrome family

PAN Xiaoxia ,CHEN Nan ,REN Hong

(Department of Nephrology,Ruijin Hospital,Shanghai Second Medical University,Shanghai 200025, China)

Abstract：Objective To find out the characteristics of mutations of gene COL4A5 encoding type Ⅳ collagen among X-linked dominant inherited Chinese Alport syndrome patients. Methods Screening for mutations in exon 43 of the COL4A5 gene was performed by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis(DGGE) analysis in 10 kindreds belong to 7 XD-AS families and 100 normal controls and their genomic DNA were analyzed by the direct sequencing. Results A point mutation was found in one family with substitution of 4142C by T which resulted in the change of the CCG codon for Pro 1314 to the codon for Set (TCG).2 male patients and their mother all had such abnormality.Conclusion Abore point mutation is an inherited gene mutation.Refer to the literature,no same gene mutation is reported.

Keywords：Alport syndrome;Polymerase chain reaction;Gel electrophoresis;COL4A5 gene

基金项目：上海市高等学校科技基金项目(97B08)；上海市卫生系统百人计划资助项目(98BR034)

参考文献：

［1］Atkin CL,Hasstedt SJ,Menlove L,et al.Mapping of Alport syndrome to the long arm of the X chromosone.Am J Hum Genet,1988,42:249-255.

［2］Zhou J,Leinonen A,Tryggvason K.Structure of the human type Ⅳ collagen COL4A5 gene.J Bio Chem,1994,269:6608-6614.

［3］Zhou J,Hertz JM,Leinonen A,et al.Complete amino acid sequence of the human α 5(Ⅳ) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient.J Bio Chem,1992,267:12475-12481.

［4］Barker DF,Hostikka SL,Zhou J,et al.Identification of mutations in the COL4A5 collagen gene in Alport syndrome.Science,1990,248:1224-1227.

［5］Renieri A,Bruttini M,Galli L,et al.X-linked Alport syndrome:an SSCP-based mutation survey over all 51 exons of the COL4A5 gene.Am J Hum Genet,1996,58:1192-1204.

［6］Kawai S,Nomura S,Harano T,et al.The COL4A5 gene in Japanese Alport syndrome patients:spectrum of mutations of all exons.Kidney Int,1996,49:814-822.

［7］Martin P,Heiskarl N,Zhou J,et al.High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.J Am Soc Nephrol,1998,9:2291-2301.

［8］丁洁,郭顺华,俞礼霞,等.用PCR-SSCP方法检测中国人Alport 综合征COL4A5 基因突变.中华儿科杂志,1999,37:473-476.

［9］Kashtan CE,Micheal AF.Alport syndrome.Kidney Int,1996,50:1445-1463.

收稿日期：2000-07-06