一个Xq部分缺失伴假肥大型肌营养不良家系的遗传学分析与产前诊断

Genetic analysis and prenatal diagnosis of Xp deletion in a family with Duchenne/Becker muscular dystrophy

目的分析一个x染色体短臂部分缺失伴Duchenne进行性肌营养不良家系Dystrophin基因的突变情况，以协助遗传咨询和产前诊断。方法综合应用染色体G显带核型分析、多重连接依赖性探针扩增、微阵列比较基因组杂交、全基因组高通量测序对该家系的部分成员进行分析。结果染色体核型显示该家系中2名女性和胎儿均为Xp部分缺失的携带者。多重连接依赖性探针扩增显示孕妇和胎儿均携带Dystrophin基因第52~79外显子缺失。微阵列比较基因组杂交、全基因组高通量测序和孕妇血浆胎儿游离DNA检测均显示孕妇及胎儿存在Xp21．1-p22．33缺失（〉30Mb）与Xq27．2-q28重复（～10Mb）。结论在该家系中，Xp部分缺失累及Dystrophin基因第52～79外显子。此外，Xp缺失造成该家系的女性携带者具有Turner综合征的特点。

Objective To delineate a deletional mutation of the Dystrophin gene on the short arm of chromosome X in a family affected with Duchenne/Becker muscular dystrophy. Methods G-banded karyotyping, multiple ligation probe amplifieation（MLPA）, array-based comparative genomic hybridization （array-CGH） and whole genome exon high-throughput sequencing were employed to delineate the mutation in the family. Results GTG handing has demonstrated deletion of the terminal part of the short arm of chromosome X in the fetus. The same ddetion was also found in its mother and maternal grandmother. MLPA analysis has revealed removal of exons 52 to 79 of the Dystrophin gene. A 30 Mb deletion in Xp22.33-p21.1 and a 10 Mh duplication in Xq27. 2-q28 were identified by array-CGH and whole genome exon high-throughput sequencing. Conclusion The Xp deletion has led to deletion of exons 52 to 79 of the Dystrophin gene in the family. The female carriers also had certain features of Turner syndrome due to the same deletion.