Daniel Art, Wu Zhanhe, Darmanian Artur, Collins Felicity, Jackson Julianne
Departments of Cytogenetics, Western Sydney Genetics Program, The Children's Hospital at Westmead, P/O Box 3515, Parramatta, NSW 2124, Australia.
Prenat Diagn. 2003 Jul;23(7):529-34. doi: 10.1002/pd.634.
Four apparent triploid/diploid mosaic cases were studied. Three of the cases were detected at prenatal diagnosis and the other was of an intellectually handicapped, dysmorphic boy. Karyotypes were performed in multiple tissues if possible, and the inheritance of microsatellites was studied with DNA from fetal tissues and parental blood. Non-mosaic triploids have a different origin from these mosaics with simple digyny or diandry documented in many cases. Three different mechanisms of origin for these apparent mosaics were detected: (1) chimaerism with karyotypes from two separate zygotes developing into a single individual, (2) delayed digyny, by incorporation of a pronucleus from a second polar body into one embryonic blastomere, and (3) delayed dispermy, similarly, by incorporation of a second sperm pronucleus into one embryonic blastomere. In three of the four cases, there was segregation within the embryos of triploid and diploid cell lines into different tissues from which DNA could be isolated. In case 2 originating by digyny, the same sperm allele at each locus could be detected in both triploid and diploid tissues, which is supportive evidence for the involvement of a single sperm and for true mosaicism rather than chimaerism. Similarly, in case 4 originating by dispermy, the same single ovum allele at each locus could be detected in diploid and triploid tissues, confirming mosaicism. In the chimaeric case (case 3), the diploid line had the karyotype 47,XY,+16 while the triploid line was 69,XXY. This suggests a chimaera, since, in a true mosaic, the triploid line should also contain the additional chromosome 16. Supporting the interpretation of a chimaeric origin for this case, the DNA data showed that the triploidy was consistent with MII non-disjunction (i.e. involving a diploid ovum). In the mosaic cases (1, 2, 4), there was no evidence of the involvement of a diploid sperm or a diploid ova, and in triploid/diploid mosaicism, an origin from a diploid gamete is excluded, since all such conceptuses would be simple triploids. In one of these triploid/diploid mosaics detected at prenatal diagnosis by CVS, the triploid line seemed to be sequestered into the extra-fetal tissues (confined placental mosaicism). This fetus developed normally and a normal infant was born with no evidence of triploidy in newborn blood or cord blood at three months of age.
对4例明显的三倍体/二倍体嵌合体病例进行了研究。其中3例在产前诊断时被检测到，另一例是一名智力障碍、畸形的男孩。如果可能的话，对多个组织进行了核型分析，并用胎儿组织和父母血液中的DNA研究了微卫星的遗传情况。非嵌合三倍体的起源与这些嵌合体不同，许多病例中记录了单纯的双雌受精或双雄受精。检测到这些明显嵌合体的三种不同起源机制：(1) 来自两个独立受精卵的核型的嵌合体发育成一个个体；(2) 延迟双雌受精，即第二个极体的原核并入一个胚胎卵裂球；(3) 延迟双精受精，同样是第二个精子原核并入一个胚胎卵裂球。在4例病例中的3例中，三倍体细胞系和二倍体细胞系在胚胎内分离到不同的可分离DNA的组织中。在由双雌受精起源的病例2中，在三倍体和二倍体组织中每个位点都能检测到相同的精子等位基因，这支持了单个精子参与以及真正的嵌合体而非嵌合体的证据。同样，在由双精受精起源的病例4中，在二倍体和三倍体组织中每个位点都能检测到相同的单个卵子等位基因，证实了嵌合体现象。在嵌合体病例（病例3）中，二倍体细胞系的核型为47,XY,+16，而三倍体细胞系为69,XXY。这表明是嵌合体，因为在真正的嵌合体中，三倍体细胞系也应该包含额外的16号染色体。支持该病例为嵌合起源的解释的是，DNA数据显示三倍体与减数第二次分裂不分离一致（即涉及二倍体卵子）。在嵌合体病例（1、2、4）中，没有证据表明二倍体精子或二倍体卵子参与其中，并且在三倍体/二倍体嵌合体中，排除了来自二倍体配子的起源，因为所有这样的孕体都将是单纯的三倍体。在通过绒毛取样产前诊断检测到的这些三倍体/二倍体嵌合体中的一例中，三倍体细胞系似乎被隔离到胎儿外组织中（局限性胎盘嵌合体）。这个胎儿发育正常，出生时是一个正常婴儿，在三个月大时新生儿血液或脐带血中没有三倍体的证据。
