Medical Genetics and Genomics Laboratory, Kaiser Permanente Southern California, Los Angeles, California, USA.
Genet Med. 2013 Jan;15(1):3-13. doi: 10.1038/gim.2012.78. Epub 2012 Aug 30.
A small supernumerary marker chromosome is often seen in patients with developmental disorders. Prior to array-based comparative genomic hybridization markers were rarely genotyped end to end. In this study, a valid genotype-to-phenotype correlation was possible because the supernumerary marker chromosomes were fully characterized by array-based comparative genomic hybridization in a genome-wide analysis.
Ten consecutive de novo small supernumerary marker chromosome cases were systematically genotyped using G-banding, C-banding, AgNOR staining, whole-genome array-based comparative genomic hybridization, and fluorescence in situ hybridization.
Among 10 small supernumerary marker chromosome cases studied, 4 (40%) were not identified by array-based comparative genomic hybridization because of low-level mosaicism or because they lacked euchromatin. One case (10%) was a simple pericentromeric marker extending from 5p13.3 to 5q11.2. Five (50%) markers showed unexpected complexity. Two cases had markers that were derivative acrocentric (AgNOR+) chromosomes with the euchromatin from chromosomes 18p or 19p. Each of the other three cases with complex markers had unusual characteristics including a marker from noncontiguous segments of chromosome 19q, a highly complex rearrangement involving a chromosome 20 homolog as well as the small supernumerary marker chromosome, and a mosaic duplication of a proximal 8p marker.
Small supernumerary marker chromosomes are frequently complex on the basis of our small sample. Whole-genome array-based comparative genomic hybridization characterization of the small supernumerary marker chromosome provided informed genetic counseling.
发育障碍患者中常可见到小的额外标记染色体。在基于阵列的比较基因组杂交技术出现之前，很少对标记染色体进行端到端的基因分型。在这项研究中，由于通过全基因组基于阵列的比较基因组杂交分析对额外标记染色体进行了全面的特征分析，因此可以实现有效的基因型-表型相关性。
对 10 例连续的新发小额外标记染色体病例进行了系统的基因分型，使用 G 带、C 带、AgNOR 染色、全基因组基于阵列的比较基因组杂交和荧光原位杂交技术。
在所研究的 10 例小额外标记染色体病例中，由于低水平嵌合体或缺乏常染色质，有 4 例（40%）未通过基于阵列的比较基因组杂交技术识别。有 1 例（10%）为简单的着丝粒标记，从 5p13.3 延伸至 5q11.2。5 个（50%）标记显示出意外的复杂性。2 例标记是衍生的近端着丝粒（AgNOR+）染色体，其常染色质来自染色体 18p 或 19p。另外 3 例具有复杂标记的病例均具有异常特征，包括来自非连续的染色体 19q 段的标记、涉及染色体 20 同源物以及小额外标记染色体的高度复杂重排，以及近端 8p 标记的镶嵌性重复。
根据我们的小样本，小额外标记染色体通常是复杂的。对小额外标记染色体进行全基因组基于阵列的比较基因组杂交特征分析提供了有针对性的遗传咨询。
