Extending the scope of diagnostic chromosome analysis: Detection of single gene defects using high-resolution SNP microarrays
Extending the scope of diagnostic chromosome analysis: Detection of single gene defects using high-resolution SNP microarrays
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DOI：
10.1002/humu.21581
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发表时间：
2011-12-01
期刊：
影响因子：
3.9
通讯作者：
Slater, Howard R.
中科院分区：
文献类型：
--
作者：
Bruno, Damien L.;Stark, Zornitza;Slater, Howard R.
微阵列分析在诊断亚显微染色体异常引起的疾病方面取得了重大进展。它已被建议，阵列测试应该是一个第一层测试在评估个人智力残疾，发育迟缓，先天性异常，自闭症。具有越来越高的探针覆盖率和分辨率的阵列的可用性增加了对基因内甚至外显子水平的递减小拷贝数变化（CNC）的检测。重要的是，对SNP进行基因分型的阵列也能检测到扩展的纯合性区域。我们描述了14例单基因疾病引起的基因内变化，从一个连续的6,500测试使用高分辨率SNP微阵列。这些病例说明了细胞遗传学检测范围的扩大，超出了通常包含许多基因的显性染色体重排。9例病例证实了临床诊断，即遵循表型到基因型的方法。其中5例是在缺乏特异性临床诊断的情况下通过实验室分析诊断的，即遵循基因型到表型的方法。2例为具有临床意义的偶然发现。精明的临床评估和实验室-临床医生咨询的重要性被强调，以优化微阵列在诊断单基因拷贝数和序列突变引起的疾病的价值。32：15001506，2011。(C)2011 Wiley Periodicals，Inc.
Microarray analysis has provided significant advances in the diagnosis of conditions resulting from submicroscopic chromosome abnormalities. It has been recommended that array testing should be a first tier test in the evaluation of individuals with intellectual disability, developmental delay, congenital anomalies, and autism. The availability of arrays with increasingly high probe coverage and resolution has increased the detection of decreasingly small copy number changes (CNCs) down to the intragenic or even exon level. Importantly, arrays that genotype SNPs also detect extended regions of homozygosity. We describe 14 examples of single gene disorders caused by intragenic changes from a consecutive set of 6,500 tests using high-resolution SNP microarrays. These cases illustrate the increased scope of cytogenetic testing beyond dominant chromosome rearrangements that typically contain many genes. Nine of the cases confirmed the clinical diagnosis, that is, followed a phenotype to genotype approach. Five were diagnosed by the laboratory analysis in the absence of a specific clinical diagnosis, that is, followed a genotype to phenotype approach. Two were clinically significant, incidental findings. The importance of astute clinical assessment and laboratory-clinician consultation is emphasized to optimize the value of microarrays in the diagnosis of disorders caused by single gene copy number and sequence mutations. 32:15001506, 2011. (C) 2011 Wiley Periodicals, Inc.