Cheung Sau W, Shaw Chad A, Scott Daryl A, Patel Ankita, Sahoo Trilochan, Bacino Carlos A, Pursley Amber, Li Jiangzhen, Erickson Robert, Gropman Andrea L, Miller David T, Seashore Margretta R, Summers Anne M, Stankiewicz Pawel, Chinault A Craig, Lupski James R, Beaudet Arthur L, Sutton V Reid
Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.
Am J Med Genet A. 2007 Aug 1;143A(15):1679-86. doi: 10.1002/ajmg.a.31740.
Somatic chromosomal mosaicism is a well-established cause for birth defects, mental retardation, and, in some instances, specific genetic syndromes. We have developed a clinically validated, targeted BAC clone array as a platform for comparative genomic hybridization (aCGH) to enable detection of a wide range of pathologic copy number changes in DNA. It is designed to provide high sensitivity to detect well-characterized submicroscopic micro-deletion and duplication disorders while at the same time minimizing detection of variation of uncertain clinical significance. In the course of studying 2,585 samples submitted to our clinical laboratory, chromosomal mosaicism was detected in 12 patient samples; 10 of these cases were reported to have had a normal blood chromosome analysis. This enhanced ability of aCGH to detect mosaicism missed by routine chromosome analysis may be due to some combination of testing multiple cell lineages and/or failure of cytogenetically abnormal T lymphocytes to respond to mitogens. This suggests that aCGH may detect somatic chromosomal mosaicism that would be missed by conventional cytogenetics.
体细胞染色体嵌合现象是导致出生缺陷、智力迟钝以及某些特定遗传综合征的一个公认原因。我们已经开发出一种经过临床验证的靶向BAC克隆阵列，作为比较基因组杂交（aCGH）的平台，以检测DNA中广泛的病理性拷贝数变化。它旨在提供高灵敏度，以检测特征明确的亚显微微缺失和微重复疾病，同时尽量减少对临床意义不确定的变异的检测。在对提交到我们临床实验室的2585份样本进行研究的过程中，在12份患者样本中检测到了染色体嵌合现象；其中10例报告显示血液染色体分析结果正常。aCGH检测常规染色体分析遗漏的嵌合现象的能力增强，可能是由于检测多个细胞谱系的某种组合和/或细胞遗传学异常的T淋巴细胞对有丝分裂原无反应。这表明aCGH可能检测到传统细胞遗传学遗漏的体细胞染色体嵌合现象。
