Weber André, Liehr Thomas, Al-Rikabi Ahmed, Bilgen Simal, Heinrich Uwe, Schiller Jenny, Stumm Markus
Medicover Genetics, MVZ Humangenetik Berlin-Lichtenberg, 13053 Berlin, Germany.
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Am Klinikum 1, 07747 Jena, Germany.
Biomedicines. 2022 May 10;10(5):1102. doi: 10.3390/biomedicines10051102.
Background: The majority of small supernumerary marker chromosomes (sSMCs) are derived from one single chromosome. Complex sSMCs instead consist of two to three genomic segments, originating from different chromosomes. Additionally, discontinuous sSMCs have been seen; however, all of them are derived from one single chromosome. Here, we reported a 41 year-old patient with infertility, hypothyroidism, rheumatism, and degenerative spine and schizoaffective disorder, being a carrier of a unique, complex, and discontinuous sSMC. Methods: The sSMC was characterized in detail by banding and molecular cytogenetics including fluorescence in situ hybridization (FISH) and array-comparative genomic hybridization (aCGH), as well as by optical genome mapping (OGM). Results: The neocentric sSMC characterized here contained seven portions of five different chromosomes and was present in ~50% of both peripheral blood cells and buccal mucosa cells. aCGH and OGM revealed gains of 8q12.3q12.3, 8q22.3−8q23.1, 9q33.3−9q34.11, 14q21.1−14q21.1, 14q21.1−14q21.2, 15q21.2−15q21.2, and 21q21.1−21q21.1. Furthermore, glass-needle based microdissection and reverse FISH, as well as FISH with locus-specific probes confirmed these results. The exact order of the involved euchromatic blocks could be decoded by OGM. Conclusions: Among the >7000 reported sSMCs in the literature, this is the only such complex, discontinuous, and neocentric marker with a centric minute shape.
大多数小额外标记染色体（sSMC）源自单一染色体。相反，复杂sSMC由两到三个基因组片段组成，起源于不同染色体。此外，还发现了不连续的sSMC；然而，它们均源自单一染色体。在此，我们报告了一名41岁的患者，患有不孕症、甲状腺功能减退症、风湿病、退行性脊柱病变和分裂情感性障碍，是一种独特、复杂且不连续的sSMC的携带者。方法：通过包括荧光原位杂交（FISH）和阵列比较基因组杂交（aCGH）在内的显带和分子细胞遗传学，以及光学基因组图谱（OGM）对sSMC进行详细表征。结果：此处表征的新着丝粒sSMC包含来自五条不同染色体的七个部分，在外周血细胞和颊黏膜细胞中均约占50%。aCGH和OGM显示8q12.3q12.3、8q22.3−8q23.1、9q33.3−9q34.11、14q21.1−14q21.1、14q21.1−14q21.2、15q21.2−15q21.2和21q21.1−21q21.1区域存在增益。此外，基于玻璃针的显微切割和反向FISH，以及使用位点特异性探针的FISH证实了这些结果。OGM可以解码所涉及的常染色质区域的确切顺序。结论：在文献中报道的7000多个sSMC中，这是唯一具有着丝粒微小形状的此类复杂、不连续且新着丝粒标记。
