应用单核苷酸多态性微阵列芯片检出一例DMD基因缺失突变胎儿

Unexpected discovery of a fetus with DMD gene deletion using single nucleotide polymorphism array

目的探讨应用单核苷酸多态性微阵列芯片 （single nucleotide polymorphism array, SNParray）检测胎儿DMD基因新发突变的价值。方法对1例发育异常、无Duchenne／Becker肌营养不良症（Duchenne/Becker muscular dystrophy,DMD/BMD）家族史的胎儿的羊水样本进行染色体核型分析及SNParray检测，之后用多重连接探针扩增（multiplex ligation-dependent probe amplification,MLPA）检测胎儿及其母亲DMD基因的缺失或重复突变。结果胎儿的羊水染色体核型为46，XY，SNParray结果为arr[hg19]Xp21．1（32455741-32571504）×1，缺失范围为116kb，其断裂点分别位于DMD基因的第16及第30内含子，范围覆盖了第17～29外显子。MLPA检测提示胎儿DMD基因存在第17-29外显子的缺失突变，但胎儿母亲DMD基因未见异常。结论胎儿DMD基因存在新发的第17～29外显子缺失突变，可能导致胎儿患BMD或DMD。对于致病基因不明、无家族病史及表型非特异的胎儿，应用SNParray检测可在一定程度上提高对于疾病的诊断效率。

Objective To investigate the value of single nucleotide polymorphism array （SNP array） for the identification of de novo mutations in the DMD gene among fetuses. Methods G-banded karyotyping and SNP array were performed on a fetus with intrauterine growth restriction but without family history of Duchenne/Becker muscular dystrophy （DMD/BMD）. Multiplex ligation-dependent probe amplification （MLPA） was subsequently applied on amniocytes and maternal peripheral blood sample to detect DMD gene deletion/duplication mutations. Results Karyotyping of amniocytes showed a normal 46, XY karyotype. SNP array on amniocytes detected a 116 kb deletion （chrX： 32 455 741-32 571 504） at Xp21. 1 with breakpoints at introns 16 and 30 respectively, encompassing exons 17-29 of the DMD gene. In addition, MLPA analysis of the DMD gene on amniocytes confirmed the deletion of exons 17 to 29 identified by SNP array. However, no deletion/duplication mutation was detected by MLPA in the mother. Conclusion The de novo deletion of exons 17 to 29 of the DMD gene detected in the fetus may result in BMD or DMD. SNP array can improve the efficiency for detecting genomic disorders in fetuses with unidentified pathogenic genes, negative family history and nonspecific phenotypes.