Kovaleva Natalia V, Cotter Philip D
Academy of Molecular Medicine, Mytniskaya str. 12/44, St. Petersburg, Russian Federation.
Department of Pediatrics, University of California San Francisco, San Francisco, CA USA.
Mol Cytogenet. 2017 Dec 11;10:45. doi: 10.1186/s13039-017-0346-0. eCollection 2017.
Mosaicism for chromosome rearrangements is common in preimplantation diagnoses, yet is rare in prenatal diagnoses as well as in other groups of patients referred to cytogenetic testing. Consequently, there is a lack of detailed studies on this kind of mosaicism in all groups of patients. Previous reports have identified a deficit of males among asymptomatic carriers of N/unbalanced Rea. Three mechanisms were proposed for explaining this phenomenon, including a high instability in the early female embryonic development, a male-specific selection against abnormal cells in the early embryo development, or a high intrauterine lethality of male carriers. To address these possibilities, we have performed a meta-analysis of male-to-female ratio (sex ratio, SR) in prenatally diagnosed and in spontaneously aborted carriers of mosaic Rea.
One hundred and twenty one prenatally detected cases of normal cell line/autosome rearrangement mosaicism (N/Rea) with known carriers' sex were identified from the literature. Carriers of N/unbalanced Rea presented with 38 abnormal and 28 normal/apparently normal outcomes while carriers of N/balanced Rea presented with 24 normal and 3 abnormal outcomes. 58% of carriers of N/unbalanced Rea with an abnormal outcome displayed a high proportion (> 50%) of amniocytes with the abnormality compared to 25% of carriers with normal/apparently normal outcome. More female carriers of N/unbalanced Rea were identified with an abnormal outcome (15 M/23F) in contrast to a notable male predominance (18 M/10F) among those with normal outcome Additionally, among spontaneously aborted carriers of N/unbalanced Rea, there was a strong female predominance (7 M/23F).
Previous reports have identified a deficit of male among asymptomatic carriers of N/unbalanced Rea. The current data suggests a male-specific selection against chromosomal abnormalities.
染色体重排的嵌合体在植入前诊断中很常见，但在产前诊断以及其他接受细胞遗传学检测的患者群体中却很少见。因此，目前缺乏对所有患者群体中此类嵌合体的详细研究。先前的报告已经确定，在N/不平衡重排的无症状携带者中男性比例较低。提出了三种机制来解释这一现象，包括女性早期胚胎发育中的高不稳定性、早期胚胎发育中针对异常细胞的男性特异性选择，或男性携带者在子宫内的高致死率。为了探究这些可能性，我们对产前诊断和自然流产的嵌合体重排携带者的男女比例（性别比例，SR）进行了荟萃分析。
从文献中确定了121例产前检测到的正常细胞系/常染色体重排嵌合体（N/Rea）病例，且已知携带者性别。N/不平衡Rea的携带者出现38例异常结果和28例正常/明显正常结果，而N/平衡Rea的携带者出现24例正常结果和3例异常结果。N/不平衡Rea且结果异常的携带者中，58%显示具有异常的羊膜细胞比例较高（>50%），而结果正常/明显正常的携带者中这一比例为25%。结果异常的N/不平衡Rea携带者中女性更多（15男/23女），而结果正常的携带者中男性明显占优势（18男/10女）。此外，在自然流产的N/不平衡Rea携带者中，女性占绝对优势（7男/23女）。
先前的报告已经确定，在N/不平衡Rea的无症状携带者中男性比例较低。目前的数据表明存在针对染色体异常的男性特异性选择。
