Hoang Sarah, Ahn Joowook, Mann Kathy, Bint Sue, Mansour Sahar, Homfray Tessa, Mohammed Shehla, Ogilvie Caroline Mackie
Cytogenetics Department, GSTS Pathology, London, UK.
Eur J Med Genet. 2011 Mar-Apr;54(2):121-9. doi: 10.1016/j.ejmg.2010.10.010. Epub 2010 Nov 5.
Mosaicism for chromosome imbalance has traditionally been detected by karyotype analysis. The introduction of array CGH into clinical diagnostic laboratories and routine clinical practice has raised concerns as to the ability of this new test to detect the presence of more than one cell line. We present our validation data on the detection of chromosome mosaicism by oligonucleotide array CGH, and the cases detected in a cohort of 3042 clinical referrals. Using an artificial mosaicism series, we found that oligonucleotide array CGH using specific analysis parameters could accurately measure levels of mosaicism down to 10% and that the degree of mosaicism could be predicted from fluorescence ratios. We detected 12 cases of mosaicism in our clinical cohort, in 9 of which there was no previous indication of mosaicism. In two cases, G-banded chromosome analysis had been carried out previously, and had failed to detect the abnormal cell line. Three cases had mosaicism for the X chromosome and 9 involved autosomes, of which 4 were mosaic for whole chromosome trisomies, one for whole chromosome monosomy, and four were mosaic for segmental imbalances. We conclude that oligonucleotide array CGH has the power to detect a range of mosaic abnormalities in clinical diagnostic samples.
传统上，染色体不平衡的嵌合体是通过核型分析来检测的。将比较基因组杂交芯片（array CGH）引入临床诊断实验室和常规临床实践引发了人们对这种新检测方法检测多种细胞系存在能力的担忧。我们展示了关于通过寡核苷酸array CGH检测染色体嵌合体的验证数据，以及在3042例临床转诊病例队列中检测到的病例。使用人工嵌合体系列，我们发现使用特定分析参数的寡核苷酸array CGH能够准确测量低至10%的嵌合水平，并且可以从荧光比率预测嵌合程度。我们在临床队列中检测到12例嵌合体病例，其中9例之前没有嵌合体的迹象。在两例病例中，之前进行过G显带染色体分析，但未能检测到异常细胞系。3例为X染色体嵌合体，9例涉及常染色体，其中4例为整条染色体三体嵌合体，1例为整条染色体单体嵌合体，4例为节段性不平衡嵌合体。我们得出结论，寡核苷酸array CGH有能力在临床诊断样本中检测一系列嵌合异常。
