Dean Nicola L, Battersby Brendan J, Ao Asangla, Gosden Roger G, Tan Seang Lin, Shoubridge Eric A, Molnar Maria Judit
Department of Obstetrics and Gynecology, Royal Victoria Hospital, Montreal, H3A 1A1, Quebec, Canada.
Mol Hum Reprod. 2003 Oct;9(10):631-8. doi: 10.1093/molehr/gag077.
To perform preimplantation genetic diagnosis for women carrying heteroplasmic mitochondrial DNA (mtDNA) mutations, it is necessary to ensure that the proportion of mutant mtDNA diagnosed in the biopsied cell gives an accurate indication of the mutant load in the remaining embryo. A heteroplasmic mouse model, carrying NZB and BALB mtDNA genotypes, was used to study the relative proportions of each mtDNA genotype in the ooplasm and first polar body of mature oocytes, and between blastomeres of early cleavage stage embryos. The levels of heteroplasmy varied widely in the gametes compared with the maternal genotype. However, the distribution of the two mtDNA genotypes was virtually identical between the ooplasm and polar body of a mature oocyte, and also between the blastomeres of each 2-, 4- and 6-8-cell embryo. Therefore, the level of heteroplasmy diagnosed from the polar body of an unfertilized oocyte or from a single blastomere of an embryo is representative of the level in the embryo as a whole. Reliable results were obtained from both polar bodies and blastomeres, but the efficiency of diagnosis was greater with blastomeres. We conclude that preimplantation genetic diagnosis is feasible for mtDNA diseases, although it should be approached with caution, as it is possible that transmission of some pathogenic mutations could behave in a different manner.
对于携带异质性线粒体DNA（mtDNA）突变的女性进行植入前基因诊断时，有必要确保在活检细胞中诊断出的突变型mtDNA比例能够准确反映剩余胚胎中的突变负荷。利用携带NZB和BALB mtDNA基因型的异质性小鼠模型，研究了成熟卵母细胞的卵质和第一极体中以及早期卵裂阶段胚胎的卵裂球之间每种mtDNA基因型的相对比例。与母本基因型相比，配子中的异质性水平差异很大。然而，成熟卵母细胞的卵质和极体之间以及每个2细胞、4细胞和6 - 8细胞胚胎的卵裂球之间，两种mtDNA基因型的分布几乎相同。因此，从未受精的卵母细胞的极体或胚胎的单个卵裂球中诊断出的异质性水平代表了整个胚胎中的水平。从极体和卵裂球都获得了可靠的结果，但卵裂球的诊断效率更高。我们得出结论，植入前基因诊断对于mtDNA疾病是可行的，尽管应该谨慎进行，因为某些致病突变的传递可能表现出不同的方式。
