染色体平衡性结构异常致9q34.3微缺失/微重复并存家系的遗传学分析

Genetic analysis of a family with 9q34.3 microdeletion and microduplication caused by abnormal chromosome balance structure

目的对1例有Kleefstra综合征患儿生育史的孕妇进行产前诊断、家系分析和遗传咨询。方法采集孕妇、孕妇丈夫和先证者外周血样以及孕中期羊水样本;应用核型分析、染色体微阵列分析(chromosomal microarray analysis,CMA)、多重连接探针扩增(multiplex ligation-dependent probe amplification,MLPA)和荧光原位杂交(fluorescence in situ hybridization,FISH)等方法寻找变异;综合家系成员情况判断变异来源,进行再发风险评估。结果所有样本核型分析均未见异常。CMA和MLPA检测提示羊水样本染色体9q34.3区段存在852 kb的3拷贝重复,结果为arr(hg19)9q34.3(140168806-141020389)×3,与患儿CMA结果提示的9q34.3微缺失片段重合;孕妇及其丈夫外周血样本未见异常。FISH检测显示孕妇染色体9q34.3片段易位至17号染色体长臂末端,结果为ish,t(9;17)(9q34.3;qter)(9p+;17p+,9q+,17q+),综合CMA和MLPA结果可知该易位为平衡性结构异常;孕妇丈夫未见异常。结论由于母亲携带平衡性单向易位,导致该家系中同胞发生染色体同一区段缺失或重复两种不同的拷贝数异常。

Objective To perform prenatal diagnosis,pedigree analysis,and genetic counseling of a pregnant woman who gave birth to a child with Kleefstra syndrome.Methods Karyotype analysis,chromosomal microarray analysis(CMA),multiplex ligation-dependent probe amplification(MLPA)and fluorescence in situ hybridization(FISH)were used of peripheral blood and amniotic fluid to find causes.Recurrence risk assessment was performed later.Results The amniotic fluid sample showed a 9q34.3 microduplication of arr(hg19)9q34.3(140168806-141020389)×3,which overlapped the 9q34.3 microdeletion region of proband.The pregnant woman was detected with a balanced translocation of ish,t(9;17)(9q34.3;qter)(9p+;17p+,9q+,17q+).No other abnormal results were found in the family.Conclusion Offspring who share the same chromosome segment deletion or duplication are always from parent who carries balanced chromosomal structural aberration.