Liehr Thomas, Williams Heather E, Ziegler Monika, Kankel Stefanie, Padutsch Niklas, Al-Rikabi Ahmed
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Am Klinikum 1, 07747, Jena, Germany.
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 622 West 168th Street, New York, NY, 10032, USA.
Mol Cytogenet. 2021 Feb 25;14(1):13. doi: 10.1186/s13039-021-00533-6.
Small supernumerary marker chromosomes (sSMCs) are additional derivative chromosomes present in an otherwise numerically and structurally normal karyotype. They may derive from each of the 24 human chromosomes, and most contain a normal centromeric region with an alphoid sequence from a single chromosome. The majority of human chromosomes have a unique centromeric DNA-sequence enabling their indubitable characterization. However, chromosomes 14 and 22 share a common centromeric sequence D14/22Z1, and sSMCs with this DNA-stretch can derive from either chromosome. Euchromatin-carrying sSMCs(14 or 22) may be further characterized by molecular cytogenetics. However, in most diagnostic laboratories, heterochromatic sSMCs cannot be differentiated between chromosomes 14 or 22 derivation and are often reported as der(14 or 22). Still, heterochromatic sSMC(14 or 22) can be distinguished from each other using the D22Z4 probe (non-commercial) localized to 22p11.2. Herein, 355 sSMC(14 or 22) analyzed in the authors' laboratory during the last ~ 20 years are summarized to address the questions: (1) What are the true frequencies of chromosome 14- and chromosome 22- derived sSMCs within D14/22Z1-positive cases? (2) Does sub-characterization of sSMC(14) and sSMC(22) make a difference in routine diagnostics? These questions could be answered as follows: (ad 1) within the studied group of sSMCs ~ 40% are derived from chromosome 14 and ~ 60% from chromosome 22; (ad 2) the knowledge on exact sSMC origin can help to save costs in routine diagnostics; i.e. in a clinically abnormal person with sSMC(14) a test for uniparental disomy is indicated, which is not necessary if a chromosome 22 origin for the sSMC was determined.
小额外标记染色体（sSMC）是在其他方面染色体数目和结构正常的核型中出现的额外衍生染色体。它们可能源自24条人类染色体中的每一条，并且大多数含有来自单一染色体的具有α卫星序列的正常着丝粒区域。大多数人类染色体具有独特的着丝粒DNA序列，从而能够对其进行明确鉴定。然而，14号和22号染色体共享一个共同的着丝粒序列D14/22Z1，具有这种DNA片段的sSMC可以源自这两条染色体中的任何一条。携带常染色质的sSMC（14或22）可以通过分子细胞遗传学进一步鉴定。然而，在大多数诊断实验室中，异染色质sSMC无法区分是源自14号还是22号染色体，通常报告为der(14或22)。尽管如此，异染色质sSMC(14或22)可以使用定位于22p11.2的D22Z4探针（非商业用途）相互区分。在此，总结了作者实验室在过去约20年中分析的355条sSMC(14或22)，以解决以下问题：（1）在D14/22Z1阳性病例中，源自14号染色体和22号染色体的sSMC的真实频率是多少？（2）sSMC(14)和sSMC(22)的亚分类在常规诊断中是否有影响？这些问题可以如下回答：（针对问题1）在所研究的sSMC组中，约40%源自14号染色体，约60%源自22号染色体；（针对问题2）关于sSMC确切起源的知识有助于在常规诊断中节省成本；即，在患有sSMC(14)的临床异常个体中，需要进行单亲二体检测，如果确定sSMC源自22号染色体，则无需进行此项检测。
