Genome-Wide Oligonucleotide Array Comparative Genomic Hybridization for Etiological Diagnosis of Mental Retardation A Multicenter Experience of 1499 Clinical Cases
Genome-Wide Oligonucleotide Array Comparative Genomic Hybridization for Etiological Diagnosis of Mental Retardation A Multicenter Experience of 1499 Clinical Cases
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DOI：
10.2353/jmoldx.2010.090115
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发表时间：
2010-03-01
影响因子：
4.1
通讯作者：
Fan, Yao-Shan
中科院分区：
文献类型：
--
作者：
Xiang, Bixia;Zhu, Hongbo;Fan, Yao-Shan
为了评估全基因组寡核苷酸阵列在精神发育迟滞诊断中的临床应用，并解决与拷贝数变化（CNCs）解释相关的问题，我们收集了来自5个学术诊断实验室的1499名先证者患者的结果，其中使用了相同的44 K阵列平台。五个实验室中有三个达到了14%的诊断率，另外两个分别为11%和7%。大约80%的异常病例有一个单一的片段缺失或重复，而其余的20%有一个复合基因组不平衡，涉及两个或更多的DNA片段。16p11.2缺失是一种常见的与智力低下相关的微缺失综合征。我们根据结构变化将致病性CNCs分为六类。我们的数据表明，44 K平台为临床使用提供了合理的分辨率，并且300 kb的大小可用作进一步研究该平台检测到的CNC的临床相关性的实际截止值。我们已经深入讨论了与阵列CGH临床使用相关的问题，并根据我们的经验为解释、报告和咨询测试结果提供了指导。（J Mol Diagn 2010，12：204-212; DOI：10.2353/jmodx.2010.090115）
To assess the clinical utility of genome-wide oligonucleotide arrays in diagnosis of mental retardation and to address issues relating to interpretation of copy number changes (CNCs), we collected results on a total of 1499 proband patients from five academic diagnostic laboratories where the same 44K array platform has been used. Three of the five laboratories achieved a diagnostic yield of 14% and the other two had a yield of 11 and 7%, respectively. Approximately 80% of the abnormal cases had a single segment deletion or duplication, whereas the remaining 20% had a compound genomic imbalance involving two or more DNA segments. Deletion of 16p11.2 is a common microdeletion syndrome associated with mental retardation. We classified pathogenic CNCs into six groups according to the structural changes. Our data have demonstrated that the 44K platform provides a reasonable resolution for clinical use and a size of 300 kb can be used as a practical cutoff for further investigations of the clinical relevance of a CNC detected with this platform. We have discussed in depth the issues associated with the clinical use of array CGH and provided guidance for interpretation, reporting, and counseling of test results based on our experience. (J Mol Diagn 2010, 12:204-212; DOI: 10.2353/jmodx.2010.090115)