Abstract:

To explore the methods of prenatal genetic diagnosis in chronic renal failure caused by WT1 mutation. Methods　Prenatal genetic diagnosis was performed on the proband’s mother after genetic consultancy. Mutation analysis of the fetus was performed on NA-based level of amniocytes. Fetus sex was determined by PCR amplification of SRY as well as karyotypes analysis. Maternal cell contamination was excluded by linkage analysis with three polymorphic microsatellite markers on X chromosome. Results　There was a WT1 IVS9+5G > A （heterozygotic） and a NPHS2 860A > G （heterozygotic） in the proband， respectively. The mother didn’t carry the WT1 IVS9+5G > A but carried the NPHS2 860A > G mutation. The father carried neither of the mutation. Amniocytes genomic DNA level based prenatal diagnosis showed that the fetus did not carry the same mutation as the mother or the proband. PCR amplification of SRY and karyotpyes analysis showed a female fetus. Linkage analysis of X chromosome polymorphic microsatellite markers showed that there was no maternal cell contamination in amniocytes. Conclusion　We have established the technique of prenatal genetics diagnosis in chronic renal failure caused by WT1 mutation in China.

Key words: Frasier syndrome, prenatal genetic diagnosis, WT1

摘要：

探讨WT1突变致慢性肾功能衰竭产前基因诊断的方法。方法　北京大学第一医院于2007年12月对1例先证者家系进行详细的遗传咨询和基因突变分析，提取患儿母亲第2胎孕20周羊水细胞基因组DNA，根据先证者基因突变分析，PCR扩增相应基因相应外显子检测胎儿突变情况， PCR扩增SRY联合核型分析检测胎儿性别，通过3个X染色体微卫星标记（AR、DXS6797和DXS6807）连锁分析除外羊水中母体细胞污染的可能。结果　先证者基因突变分析结果为WT1基因IVS9+5G >A杂合突变，同时合并NPHS2第7外显子g. 860A > G杂合突变。核型分析显示，患儿核型为46 XY。家系突变分析显示，患儿母亲携带NPHS2第7外显子g. 860A > G杂合突变，无WT1基因IVS9+5G > A杂合突变，父亲未发现异常。患儿母亲第2胎产前羊水细胞基因组DNA检测显示，胎儿无WT1和NPHS2相应位点突变。PCR扩增SRY基因和核型分析均显示胎儿为女性，连锁分析显示羊水细胞中无母体细胞污染。结论　本研究建立了WT1突变所致慢性肾衰竭产前基因诊断的方法。

关键词: Frasier综合征, 产前基因诊断, WT1