三个肾上腺脑白质营养不良家系的产前分子诊断

目的对3名来自不同家系的肾上腺脑白质营养不良(ALD)携带者所怀胎儿进行产前分子诊断。方法在采用STR位点分析方法排除母体基因组DNA污染后,分别应用变性高效液相色谱和DNA测序方法对3个胎儿的羊水基因组DNA进行分析。结果胎儿1和携带者1的分析结果完全一样,均出现洗脱双峰,并经DNA测序证实,该胎儿为S108X突变携带者；胎儿2、胎儿3和正常对照一致,均为洗脱单峰,经DNA测序证实,这两个胎儿的基因组DNA上均不存在基因突变(R617C突变和1801．02del AG突变)。结论胎儿1带S108X突变,为ALD携带者；胎儿2不带R617C突变,为正常纯合子；胎儿3不带1801—02del AG突变,为正常半合子。

Prenatal molecular diagnosis of 3 Chinese X-linked adrenoleukodystrophy pedigrees

Objective To carry out prenatal molecular diagnosis on 3 fetuses from different pedigrees with X-linked adrenoleukodystrophy (ALD).Methods The anmiotic fluid was obtained with the help of a clinical doctor and the genomic DNA was isolated from it.Maternal DNA contamination was excluded by fluorescent STR profiling.The S108X,R617C and 1801-02 del AG mutations found in the 3 different pedigrees were searched in genomic DNA of amniotic fluid cells (AFC) from 3 fetuses by denaturing high performance liquid chromatography (DHPLC) and DNA direct sequencing.Results Two different eluting peaks were detectable from the genomic DNA of the fetus 1 and her mother using DHPLC but not from that of the fetus's father and unrelated controls.S108X mutation was found in one allele of the fetus and her mother using DNA direct sequencing.One eluting peak was visualized in the genomic DNA of the fetus 2 and 3 using DHPLC,which was identical to those from the DNA of their fathers and controls. R617C mutation or 1801-02 del AG mutation was not detectable in their genomic DNA.Conclusion Fetus 1 had S108X mutation on her ABCD1 gene and she was an ALD cartier.Fetus 2 had no R617C mutation on her A BCD1 gene and she was a normal homozygote.Fetus 3 had no 1801-02 del AG mutation on his ABCD1 gene and he was a normal hemizygote.