Live births following preimplantation genetic testing for dynamic mutation diseases by karyomapping: a report of three cases
Live births following preimplantation genetic testing for dynamic mutation diseases by karyomapping: a report of three cases
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通过核型定位进行动态突变疾病植入前基因检测后的活产：三例报告
DOI：
10.1007/s10815-020-01718-5
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发表时间：
2020-03-02
影响因子：
3.1
通讯作者：
Sun, Yingpu
中科院分区：
文献类型：
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作者：
Shi, Dayuan;Xu, Jiawei;Sun, Yingpu
目的对孟德尔遗传病患者进行植入前单基因缺陷检测（PGT-M）是一种有益的策略，可保护其后代不遗传该疾病。本研究的目的是报告的有效性PGT-M的基础上karyomapping为三例动态突变疾病的三核苷酸重复expansion.MethodsPGT-M进行了三对夫妇，其家庭成员被诊断为亨廷顿舞蹈病或脊髓小脑共济失调2或12。采用多重置换扩增（MDA）方法进行全基因组扩增。然后，进行核型分析，以检测等位基因是携带三核苷酸重复扩增使用单核苷酸多态性（SNP）连锁分析，并拷贝数变异（CNVs）的胚胎也被确定。结果3对夫妇均成功进行了PGT-M，并接受了无相关致病等位基因的整倍体囊胚移植。三个家系均获得临床妊娠，产前诊断证实了核型图的有效性。这三个出生的婴儿是健康的和免费的致病等位基因HTT，ATXN 2，或PPP 2 R2 B对应的亨廷顿氏病，脊髓小脑共济失调2或12，分别。在这项工作中，我们首次报告了健康婴儿的出生，这些婴儿不含通过核型分析接受PGT-M的患者中动态突变疾病的致病基因。
PurposeThe preimplantation genetic testing for monogenic defects (PGT-M) is a beneficial strategy for the patients suffering from a Mendelian disease, which could protect their offspring from inheriting the disease. The purpose of this study is to report the effectiveness of PGT-M based on karyomapping for three cases of dynamic mutation diseases with trinucleotide repeat expansion.MethodsPGT-M was carried out on three couples, whose family members were diagnosed with Huntington’s disease or spinocerebellar ataxias 2 or 12. The whole genome amplification was obtained using the multiple displacement amplification (MDA) method. Then, karyomapping was performed to detect the allele that is carrying the trinucleotide repeat expansion using single nucleotide polymorphism (SNP) linkage analyses, and the copy number variations (CNVs) of the embryos were also identified. Prenatal diagnosis was performed to validate the accuracy of PGT-M.ResultsPGT-M was successfully performed on the three couples, and they accepted the transfers of euploid blastocysts without the relevant pathogenic allele. The clinical pregnancies were acquired and the prenatal diagnosis of the three families confirmed the effectiveness of karyomapping. The three born babies were healthy and free of the pathogenic allelesHTT,ATXN2, orPPP2R2Bcorresponding to Huntington’s disease, spinocerebellar ataxias 2 or 12, respectively.ConclusionThis study shows that karyomapping is a highly powerful and efficient approach for dynamic mutation detection in preimplantation embryos. In this work, we first report the birth of healthy babies that are free of the pathogenic gene for dynamic mutation diseases in patients receiving PGT-M by karyomapping.