Zhang Sufen, Zhou Yuqiu, Xiao Gefei, Qiu Xianrong
Department of Clinical Laboratory (Institute of Medical Genetics), Zhuhai Center for Maternal and Child Health Care, Zhuhai, Guangdong, China.
Mol Genet Genomic Med. 2023 Oct;11(10):e2229. doi: 10.1002/mgg3.2229. Epub 2023 Jun 20.
The identification of genetic mosaicism and the genetic counseling needed following its discovery have been challenging problems in the field of prenatal diagnosis. Herein, we describe the clinical phenotypes and various prenatal diagnostic processes used for two rare cases of 9p duplication mosaicism and review the prior literature in the field to evaluate the merits of different methods for diagnosing mosaic 9p duplication.
We recorded ultrasound examinations, reported the screening and diagnosis pathways, and analyzed the mosaic levels of the two cases of 9p duplication using karyotype analysis, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization analysis (FISH).
Case 1 had a normal clinical phenotype for tetrasomy 9p mosaicism, and Case 2 showed multiple malformations caused by both trisomy 9 and trisomy 9p mosaicism. Both cases were initially suspected after non-invasive prenatal screening (NIPT) based on cell-free DNA. The mosaic ratio of 9p duplication found via karyotyping was lower than what was discovered by CMA and FISH, in both cases. Contrary to previous findings, the mosaic level of trisomy 9 found by karyotype analysis was greater than what was found by CMA, in terms of complex mosaicism involving trisomy 9 and trisomy 9p, in Case 2.
NIPT can indicate 9p duplication mosaicism during prenatal screening. Different strengths and limitations existed in terms of diagnosing mosaic 9p duplication by karyotype analysis, CMA, and FISH. The combined use of various methods may be capable of more accurately determining break-points and mosaic levels of 9p duplication during prenatal diagnosis.
基因镶嵌现象的识别以及发现该现象后所需的遗传咨询一直是产前诊断领域的难题。在此，我们描述了两例罕见的9号染色体短臂重复镶嵌现象的临床表型和各种产前诊断过程，并回顾该领域的既往文献，以评估诊断9号染色体短臂重复镶嵌现象不同方法的优缺点。
我们记录了超声检查情况，报告了筛查和诊断途径，并使用核型分析、染色体微阵列分析（CMA）和荧光原位杂交分析（FISH）对两例9号染色体短臂重复病例的镶嵌水平进行了分析。
病例1的9号染色体短臂四体镶嵌现象具有正常的临床表型，病例2表现出由9号染色体三体和9号染色体短臂三体镶嵌现象导致的多种畸形。两例最初都是在基于游离DNA的无创产前筛查（NIPT）后被怀疑。在这两例中，通过核型分析发现的9号染色体短臂重复的镶嵌比例均低于CMA和FISH所发现的比例。与之前的发现相反，就病例2中涉及9号染色体三体和9号染色体短臂三体的复杂镶嵌现象而言，通过核型分析发现的9号染色体三体的镶嵌水平高于CMA所发现的水平。
无创产前筛查在产前筛查期间可提示9号染色体短臂重复镶嵌现象。在通过核型分析、CMA和FISH诊断9号染色体短臂重复镶嵌现象方面存在不同的优势和局限性。多种方法联合使用可能能够在产前诊断期间更准确地确定9号染色体短臂重复的断点和镶嵌水平。
