Denys-Drash综合征及其致病基因突变鉴定二例报道

Study of the WT1 gene mutation in the Chinese patients with Denys-Drash syndrome

目的研究中国Denys-Drash综合征(DDS)患者Wilms瘤基因1(WT1)的基因突变。方法应用PCR方法扩增出WT1基因全部10个外显子及其相邻内含子序列,经纯化后进行PCR产物直接测序。结果2例患者WT1基因分别存在1个杂合错义突变。例1的X外显子9第1180位碱基C-→T突变,造成第394位精氨酸改变为色氨酸,即p．R394W(c．1180C> T)。例号2的S外显子9第1203位碱基C→A突变,造成第401位组氨酸改变为谷氨酰胺,即p．H401Q(c．1203C>A)。其中第1203位碱基C→A突变,p．H401Q(c．1203C>A),在国内外文献及突变数据库中均未见报道,属新发现的突变。结论DDS综合征WT1基因中外显子9为突变热点,并发现一种新的WT1基因突变。

Objective To investigate the mutations of WT1 gene in Chinese patients with Denys-Drash syndrome （DDS）. Methods Peripheral blood samples were collected from two children diagnosed clinically as DDS and genomic DNA was isolated from all blood samples using routine method. All ceding WT1 exons and their flanking intronic sequences were amplified by polymerase chain reaction （PCR）. The amplified PCR products from all individuals were then subjected to automatic DNA sequencing. Results Two types of heterozygous missense mutations in the WT1 gene were： （1）c.1180 C to T transition in exon 9,resulting in replacement of an arginine residue by tryptophan （c.1180C：〉T, p.R394W）.（2）c.1203 C to T transition in exon 9, resulting in replacement of a histidine residue by glutamine（c.1203C〉A, p.H401Q）. It is the first time that c.1203C〉A （p.H401Q） mutation was reported. Conclusions Two mutations including a novel missense mutations （c.1203C〉A, p.H401Q） in the WT1 gene are identified in two Chinese children with DDS. Our data also support that the WT1 in DDS locates at c.1180C〉T, p.R394W in exon 9.