Al-Rikabi Ahmed B Hamid, Pekova Sona, Fan Xioabo, Jančušková Tereza, Liehr Thomas
Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Am Klinikum 1, 07747Jena, Germany.
Synlab Genetics s.r.o., Evropska 176/16, 16000 Prague 6, Czech Republic.
Curr Genomics. 2018 Apr;19(3):192-199. doi: 10.2174/1389202918666170717163830.
Cytogenetically visible chromosomal imbalances in humans are deleterious and adverse in the majority of the cases. However, healthy persons living with chromosomal imbalances in the range of several megabasepairs (Mbps) in size, like carriers of small Supernumerary Marker Chromosomes (sSMCs) exist.
MATERIALS & METHODS: The identification of healthy sSMC carriers with euchromatic centromere-near (ECN) imbalances led to the following proposal: ECN-regions do not contain any dosage sensitive genes. Due to own previous work, dosage-insensitive pericentric ECN-regions were already determined with an accuracy of 0.3 and 5 Mbp. Based on this data we established 43 new pericentromeric probe sets spanning about 3-5 Mbp of each euchromatic human chromosome arm starting from the known insensitive regions towards distal. Such so called pericentromeric-critical region fluorescence in situ hybridization (PeCR-FISH) probe sets were applied exemplarily and successful here in 15 sSMC cases as available from the Else Kröner-Fresenius-sSMC-cellbank http://ssmc-tl.com/ekf-cellbank.html.
Most of the involved sSMC breakpoints could be characterized as a higher resolution than before. An unexpected result was that in 5/15 cases cryptic mosaicism was characterized. The latter is also to be considered to have potentially an influence on the clinical outcome in these so-called discontinuous sSMCs. Overall, the suitability of PeCR-FISH to characterize sSMCs was proven; the potential of this probe set to further delineate sizes of dosage insensitive pericentric regions is obvious but dependent on suited cases. Furthermore, discontinuous sSMCs can be identified by this approach and this new subtype of sSMC needs to be studied in more detail in future.
在大多数情况下，人类细胞遗传学上可见的染色体失衡是有害且不利的。然而，确实存在一些健康人携带着大小在几兆碱基对（Mbps）范围内的染色体失衡，例如小额外标记染色体（sSMC）携带者。
对具有常染色质着丝粒近端（ECN）失衡的健康sSMC携带者的鉴定得出了以下结论：ECN区域不包含任何剂量敏感基因。基于我们之前的工作，已经确定了剂量不敏感的近着丝粒ECN区域，其精度为0.3和5 Mbp。基于这些数据，我们从已知的不敏感区域向远端延伸，为每条人类常染色质染色体臂建立了43个新的近着丝粒探针组，每组跨度约3 - 5 Mbp。这种所谓的近着丝粒关键区域荧光原位杂交（PeCR - FISH）探针组在此处被示例性地应用于来自Else Kröner - Fresenius - sSMC细胞库<http://ssmc - tl.com/ekf - cellbank.html>的15例sSMC病例中，并取得了成功。
与之前相比，大多数涉及的sSMC断点能够以更高的分辨率进行特征描述。一个意外的结果是，在15例病例中有5例表现出隐匿性嵌合现象。在这些所谓的不连续sSMC中考虑到后者可能对临床结果有潜在影响。总体而言，PeCR - FISH用于表征sSMC的适用性得到了证实；该探针组进一步描绘剂量不敏感近着丝粒区域大小的潜力是明显的，但取决于合适的病例。此外，通过这种方法可以识别不连续sSMC，并且这种新的sSMC亚型未来需要更详细地研究。
