标题：Preimplantation genetic diagnosis for a carrier with m.3697G>A mitochondrial DNA mutation
中文标题：胚胎植入前遗传筛选线粒体脱氧核糖核酸m.3697G>A 突变的携带者
引用信息：Ji D, Li X, Pan J, Zong K, Chen D, Marley JL, Zou W, Deng X, Cao Y, Zhang Z, Zhou P, Sha H, Cao Y. Preimplantation genetic diagnosis for a carrier with m.3697G > A mitochondrial DNA mutation. J Assist Reprod Genet. 2021 Dec;38(12):3251-3260. doi: 10.1007/s10815-021-02354-3. Epub 2021 Nov 21. PMID: 34802141; PMCID: PMC8666394.
摘要：
Objective:To explore inheritance of the m.3697G > A mitochondrial DNA (mtDNA) mutation and the effectiveness of preimplantation genetic diagnosis (PGD) for the carrier.
Methods:The study encompassed a pedigree of m.3697G > A mtDNA mutation, including one asymptomatic patient who pursued for PGD treatment. Twelve cumulus oocyte complexes (COCs) were collected in the first PGD cycle and 11 COCs in the second cycle. The efficiency of cumulus cells, polar bodies, and trophectoderm (TE) in predicting the m.3697G > A heteroplasmy of embryos was analyzed.
Results:From 23 COCs, 20 oocytes were fertilized successfully. On day 5 and 6 post-fertilization, 15 blastocysts were biopsied. The m.3697G > A mutation load of TE biopsies ranged from 15.2 to 100%. In the first cycle, a blastocyst with mutation load of 31.7% and chromosomal mosaicism was transferred, but failed to yield a clinical pregnancy. In the second cycle, a euploid blastocyst with mutation load of 53.9% was transferred, which gave rise to a clinical pregnancy. However, the pregnancy was terminated due to fetal cleft lip and palate. The mutation loads of different tissues (47.7 ± 1.8%) from the induced fetus were comparable to that of the biopsied TE and amniotic fluid cell (49.7%). The mutation load of neither cumulus cells (R2= 0.02, p = 0.58) nor polar bodies (R2= 0.33, p = 0.13) correlated with TE mutation load which was regarded as a gold standard.
Conclusions:The m.3697G > A mutation showed a random pattern of inheritance. PGD could be used to reduce the risk of inheritance of a high mutation load. Cumulus cells are not a suitable predictor of blastocyst mutation load.
中文摘要：
目的: 探讨 m. 3697G > A 型线粒体脱氧核糖核酸(mtDNA)基因突变的遗传规律及胚胎植入前遗传筛选(PGD)对该携带者的治疗效果。
方法: 该研究包括 m.3697 G > A mtDNA 突变的家系，包括一名无症状的 PGD 患者。在第一个 PGD 周期收集了十二个卵丘卵母细胞复合体(coCs) ，在第二个周期收集了11个。分析了卵丘细胞、极体和滋养外胚层(TE)预测胚胎 m. 3697G > A 异质性的效率。
结果: 23个卵母细胞中有20个成功受精。受精后第5天和第6天，对15个囊胚进行活检。TE 活检组织的 m. 3697G > A 突变负荷在15.2% ~ 100% 之间。在第一个周期，突变负荷为31.7% 和染色体镶嵌的囊胚被转移，但未能产生临床妊娠。在第二个周期中，转移了一个突变负荷为53.9% 的整倍体囊胚，导致临床妊娠。然而，由于胎儿唇颚裂的原因终止了妊娠。诱导胎儿不同组织的突变负荷(47.7 ± 1.8%)与活检组织和羊水细胞的突变负荷(49.7%)相当。卵丘细胞(R2 = 0.02，p = 0.58)和极体(R2 = 0.33，p = 0.13)的突变负荷与被视为金标准的 TE 突变负荷相关。
结论: m. 3697G > A 突变为随机遗传。PGD 可以用来降低高突变负荷的遗传风险。卵丘细胞不是一个合适的预测囊胚突变负荷。
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