Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases.
Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases.
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染色体微阵列分析的临床实施：2513例产后病例的摘要。
DOI：
10.1371/journal.pone.0000327
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发表时间：
2007-03-28
期刊：
影响因子：
3.7
通讯作者：
Ward, Patricia A.
中科院分区：
文献类型：
--
作者：
Lu, Xinyan;Shaw, Chad A.;Patel, Ankita;Li, Jiangzhen;Cooper, M. Lance;Wells, William R.;Sullivan, Cathy M.;Sahoo, Trilochan;Yatsenko, Svetlana A.;Bacino, Carlos A.;Stankiewicz, Pawel;Ou, Zhishu;Chinault, A. Craig;Beaudet, Arthur L.;Lupski, James R.;Cheung, Sau W.;Ward, Patricia A.
阵列比较基因组杂交（a-CGH）是检测基因组失衡、研究疾病机制和发病机制的有力分子细胞遗传学工具。我们报告我们的经验与临床实施这种高分辨率的人类基因组分析，称为染色体微阵列分析（CMA）。CMA临床上进行了2513产后样本的患者涉及各种临床表型。最初的775个样品使用CMA阵列版本4进行研究，剩余的1738个样品使用含有扩大的基因组覆盖的CMA版本5进行分析。总体而言，CMA在8.5%的患者中确定了临床相关的基因组失衡：V4为7.6%，V5为8.9%。在117例已知的细胞遗传学可检测的重排的额外调查中，CMA确定了大多数（92.5%）的基因组不平衡。重要的是，在5.2%（98/1872）核型/FISH结果正常的患者中观察到异常CMA结果，而V5扩大了基因组覆盖范围，使该类别的检出率高于V4。对于无可用细胞遗传学结果的病例，检测到8.0%（42/524）的CMA结果异常; V5再次证明检测异常的能力增加。CMA的诊断潜力提高了90例，其中51个隐藏的微缺失和39个预测的明显的相互微重复，在13个特定的染色体区域与11个已知的基因组疾病。此外，CMA确定了262个先证者的不确定意义的拷贝数变异（CNVs）;然而，父母的研究通常有利于临床解释。其中，217例被解释为家族性变异，11例被确定为新发变异;其余34例等待亲本研究以解决临床意义。这一系列的临床结果表明，CMA检测临床相关基因组失衡的灵敏度显著提高，并强调需要全面的遗传咨询，以促进准确的临床相关性和解释。
Array Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism and pathogenesis. We report our experience with the clinical implementation of this high resolution human genome analysis, referred to as Chromosomal Microarray Analysis (CMA). CMA was performed clinically on 2513 postnatal samples from patients referred with a variety of clinical phenotypes. The initial 775 samples were studied using CMA array version 4 and the remaining 1738 samples were analyzed with CMA version 5 containing expanded genomic coverage. Overall, CMA identified clinically relevant genomic imbalances in 8.5% of patients: 7.6% using V4 and 8.9% using V5. Among 117 cases referred for additional investigation of a known cytogenetically detectable rearrangement, CMA identified the majority (92.5%) of the genomic imbalances. Importantly, abnormal CMA findings were observed in 5.2% of patients (98/1872) with normal karyotypes/FISH results, and V5, with expanded genomic coverage, enabled a higher detection rate in this category than V4. For cases without cytogenetic results available, 8.0% (42/524) abnormal CMA results were detected; again, V5 demonstrated an increased ability to detect abnormality. Improved diagnostic potential of CMA is illustrated by 90 cases identified with 51 cryptic microdeletions and 39 predicted apparent reciprocal microduplications in 13 specific chromosomal regions associated with 11 known genomic disorders. In addition, CMA identified copy number variations (CNVs) of uncertain significance in 262 probands; however, parental studies usually facilitated clinical interpretation. Of these, 217 were interpreted as familial variants and 11 were determined to be de novo; the remaining 34 await parental studies to resolve the clinical significance. This large set of clinical results demonstrates the significantly improved sensitivity of CMA for the detection of clinically relevant genomic imbalances and highlights the need for comprehensive genetic counseling to facilitate accurate clinical correlation and interpretation.
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