Department of Biology and Medical Genetics, Charles University, 2nd Faculty of Medicine and University Hospital Motol, V Uvalu 84, Prague, Czech Republic.
N Biotechnol. 2012 Feb 15;29(3):321-4. doi: 10.1016/j.nbt.2010.10.006. Epub 2010 Oct 20.
Developmental delay is often a predictor of mental retardation (MR) or autism, two relatively frequent developmental disorders severely affecting intellectual and social functioning. The causes of these conditions remain unknown in most patients. They have a strong genetic component, but the specific genetic defects can only be identified in a fraction of patients. Recent developments in genomics supported the establishment of the causal link between copy number variants in the genomes of some patients and their affection. One of the techniques suitable for this analysis is array comparative genome hybridization, which can be used both for detailed mapping of chromosome rearrangements identified by classical cytogenetics and for the identification of novel submicroscopic gains or losses of genetic material. We illustrate the power of this approach in two patients. Patient 1 had a cytogenetically visible deletion of chromosome X and the molecular analysis was used to specify the gene content of the deletion and the prognosis of the child. Patient 2 had a seemingly normal karyotype and the analysis revealed a small recurrent deletion of chromosome 1 likely to be responsible for his phenotype. However, the genetic dissection of MR and autism is complicated by high heterogeneity of the genetic aberrations among patients and by broad variability of phenotypic effects of individual genetic defects.
发育迟缓通常是智力障碍（MR）或自闭症的预测指标，这两种疾病都是严重影响智力和社交功能的常见发育障碍。在大多数患者中，这些疾病的病因仍然未知。它们具有很强的遗传成分，但特定的遗传缺陷只能在一小部分患者中确定。基因组学的最新进展支持了一些患者基因组中的拷贝数变异与其疾病之间存在因果关系。适用于这种分析的技术之一是阵列比较基因组杂交，它既可以用于通过经典细胞遗传学鉴定的染色体重排的详细作图，也可以用于鉴定新的亚微观遗传物质的增益或缺失。我们通过两个患者的例子来说明这种方法的作用。患者 1 具有染色体 X 的可见缺失，分子分析用于指定缺失的基因内容和儿童的预后。患者 2 具有看似正常的核型，分析显示可能导致其表型的 1 号染色体小的重复缺失。然而，MR 和自闭症的遗传剖析受到患者之间遗传异常的高度异质性以及单个遗传缺陷的表型效应的广泛可变性的复杂化。
