Department of Paediatrics, Peking University First Hospital, Beijing, China.
Nephrology (Carlton). 2011 May;16(4):377-80. doi: 10.1111/j.1440-1797.2010.01438.x.
Alport syndrome (AS) is a progressive renal disease characterized by haematuria and progressive renal failure. An accurate genetic diagnosis of AS is very important for genetic counselling and even prenatal diagnosis.
We detected mutation of COL4An by amplifying the entire coding sequence mRNA of peripheral blood lymphocytes using polymerase chain reaction (PCR) in five Chinese AS families who asked for genetic counselling and prenatal diagnosis, then performed prenatal genetic diagnosis for four families. Mutation analysis of the foetus was made using DNA extracted from amniocytes. Foetus sex was determined by PCR amplification of SRY as well as karyotype analysis. Maternal cell contamination was excluded by linkage analysis.
Four different COL4A5 gene variants and two COL4A3 gene variants were detected in the five families. Because there was a de novo mutation in family 2, prenatal diagnosis was performed for the other four families. Results showed a normal male foetus for family 1 and family 4, respectively. Results showed an affected male foetus for families 3 and 5, and the pregnancies were terminated.
An easier, faster and efficacious method for COL4An gene mutation screening based on mRNA analysis from peripheral blood lymphocytes was established. Prenatal genetic diagnosis was performed in four AS families in China.
Alport 综合征（AS）是一种进行性肾脏疾病，其特征为血尿和进行性肾功能衰竭。对 AS 进行准确的基因诊断对于遗传咨询甚至产前诊断非常重要。
我们通过聚合酶链反应（PCR）扩增外周血淋巴细胞的整个编码序列 mRNA，对 5 个寻求遗传咨询和产前诊断的中国 AS 家系进行了 COL4An 突变检测，然后对 4 个家系进行了产前遗传诊断。使用从羊水细胞中提取的 DNA 对胎儿进行突变分析。通过 PCR 扩增 SRY 以及核型分析来确定胎儿的性别。通过连锁分析排除母体细胞污染。
在这 5 个家系中检测到 4 种不同的 COL4A5 基因突变和 2 种 COL4A3 基因突变。由于 2 号家系存在新生突变，因此对其他 4 个家系进行了产前诊断。结果显示，1 号和 4 号家系分别为正常男性胎儿。结果显示 3 号和 5 号家系为受累男性胎儿，妊娠终止。
建立了一种基于外周血淋巴细胞 mRNA 分析的 COL4An 基因突变筛查更简单、快速、有效的方法。在中国对 4 个 AS 家系进行了产前遗传诊断。
