Array-based comparative genome hybridization in clinical genetics
Array-based comparative genome hybridization in clinical genetics
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DOI：
10.1203/01.pdr.0000233012.00447.68
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发表时间：
2006-09-01
影响因子：
3.6
通讯作者：
Orr-Urtreger, Avi
中科院分区：
文献类型：
--
作者：
Bar-Shira, Anat;Rosner, Guy;Orr-Urtreger, Avi
DNA拷贝数异常常见于患有多种异常综合征和精神发育迟滞的患者。基于阵列的比较基因组杂交 (array-CGH) 是一种高分辨率的全基因组技术，可改进对这些综合征背后的亚显微畸变的检测。使用 GenoSensor Array 300 芯片对 8 名患有精神残疾、多种先天性异常和畸形特征的患者进行了亚微观染色体失衡筛查。先前通过荧光原位杂交（FISH）分析检测到的亚端粒畸变在两名患者中得到证实，并为两名先前未诊断的复杂病例提供了准确的诊断。在患有肌张力低下、隐睾和色素沉着不足的新生儿中检测到 15q11.2-q13 的微缺失，芯片结果与 FISH 分析之间几乎没有差异。在一名先前未确诊的男孩中发现了 22q11.2 处 GSCL、HIRA 和 TBX1 基因的连续微缺失，该男孩的 VCF/DiGeorge 谱有异常表现。在患有无虹膜的新生儿中，观察到了临界假阴性 WT1 缺失，很可能是因为基因组缺失的大小与微阵列探针之间存在差异。逐个克隆分析的假阳性率为 0.2%，而每个患者的假阳性率为 20%。 Array-CGH 是快速准确检测与拷贝数异常相关的遗传性疾病的强大工具，可显着改善临床遗传诊断和护理。
Abnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes and mental retardation. Array-based comparative genomic hybridization (array-CGH) is a high-resolution, whole-genome technology that improves detection of submicroscopic aberrations underlying these syndromes. Eight patients with mental disability, multiple congenital anomalies, and dysmorphic features were screened for submicroscopic chromosomal imbalances using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2-q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with aniridia, a borderline false-negative WT1 deletion was observed, most probably because of differences between the size of the genomic deletion and the microarray probe. A false-positive rate of 0.2% was calculated for clone-by-clone analysis, whereas the per patient false-positive rate was 20%. Array-CGH is a powerful tool for the rapid and accurate detection of genetic disorders associated with copy number abnormalities and can significantly improve clinical genetic diagnosis and care.