Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies
Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies
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DOI：
10.1016/j.ajhg.2010.04.006
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发表时间：
2010-05-14
影响因子：
9.8
通讯作者：
Ledbetter, David H.
中科院分区：
文献类型：
--
作者：
Miller, David T.;Adam, Margaret P.;Ledbetter, David H.
染色体微阵列分析（CMA）越来越多地用于对患有不明原因的发育迟缓/智力残疾（DD/ID）、自闭症谱系障碍（ASD）或多种先天性异常（MCA）的个体进行基因检测。对每位患者都进行CMA和G显带核型分析会大幅增加基因检测的总成本。国际标准细胞基因组阵列（ISCA）联盟举办了两次国际研讨会，并对33项研究进行了文献综述，其中包括21698名接受CMA检测的患者。我们提供了一份基于证据的临床细胞遗传学检测总结，就技术优势和局限性、各种染色体畸变的诊断率以及影响检测结果解读的问题，对CMA和G显带核型分析进行了比较。对于患有不明原因的DD/ID、ASD或MCA的个体进行基因检测，CMA的诊断率（15% - 20%）比G显带核型分析（约3%，不包括唐氏综合征和其他可识别的染色体综合征）高得多，这主要是因为CMA对亚显微缺失和重复更为敏感。真正的平衡重排和低水平嵌合体通常无法通过阵列检测到，但这些在该人群中是相对罕见的异常表型病因（
Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (