激素耐药型肾病综合征单卵孪生姐妹WT1基因突变

Mutation of WT1 Gene in Female Monozygotic Twins with Steroid-Resistant Nephrotic Syndrome

目的分析1个汉族激素耐药型肾病综合征(SRNS)家系WT1基因突变及其特点。方法研究对象为1个汉族SRNS家系先证者及其单卵孪生姐姐、父母和大姐;健康对照人群为50例尿检正常的汉族成年人。取所有研究对象外周静脉血3 mL,提取基因组DNA,PCR扩增WT1基因全部10个外显子及其周围的部分内含子序列,对PCR产物直接进行DNA序列测定。结果先证者患儿临床表型为不完全型Denys-Drash综合征,其孪生姐姐临床表型为孤立性SRNS。在该对单卵孪生姐妹中均检测到WT1基因1180C>T(R394W)杂合突变,在先证者父母及其大姐和50例健康对照人群未检测到该突变;此外,还在对该孪生姐妹检测到3个相同的WT1基因多态性——126C>T、903A>G和IVS7-32C>A。结论本研究在1个汉族SRNS家系临床表型不同的单卵孪生姐妹中发现了相同的WT1基因R394W杂合突变。

Objective To examine the mutations in the WT1 gene in a family with steroid-resistant nephrotic syndrome（SRNS） in Chinese Han ethnic group. Methods Peripheral blood samples were collected for genetic analysis from female monozygotic twins and their parents,as well as older sister.Fifty unrelated adult volunteers in Chinese Han ethnic group whose urinalysis were normal were studied as controls.Genomic DNA was isolated from peripheral blood leucocytes.All exons and exon-intron boundaries of the WT1 gene were amplified by polymerase chain reaction.Mutational analysis was performed by direct DNA sequencing. Results The twins presented incomplete Denys-Drash syndrome and isolated SRNS,respectively.A heterozygous mutation 1180CT in the WT1 gene,resulting in an arginine-to-tryptophan（R394W） substitution,was identified in both twins,whereas it was not found in their parents or older sister or the 50 controls.Moreover,three WT1 polymorphisms,126CT,903AG,and IVS7-32CA,were also found in the twins. Conclusion An identical mutation in the WT1 gene,R394W,is identified in both twins who showed different clinical phenotypes.