Zrnová E, Vranová V, Slámová I, Gaillyová R, Kuglík P
University Hospital Brno, Department of Medical Genetics, Integrated Laboratory of Molecular Cytogenetics, Brno, Czech Republic.
Folia Biol (Praha). 2011;57(5):206-15.
Submicroscopic structural chromosomal aberrations (microduplications and microdeletions) are believed to be common causes of mental retardation. These so-called copy number variations can now be routinely detected using various platforms for array-based comparative genomic hybridization (array-CGH), which allow genome-wide identification of pathogenic genomic imbalances. In this study, oligonucleotide-based array-CGH was used to investigate a panel of 23 patients with mental retardation and developmental delay, dysmorphic features or congenital anomalies. Array-CGH confirmed or revealed 16 chromosomal aberrations in a total of 12 patients. Analysis of parental samples showed that five aberrations had occurred de novo: del(1)(p36.33p36.23), del(4)(p16.3p16.2) joined with dup(8)(p23.3p23.1), del(6)(q14.1q15), del(11)(q13.1q13.4). Three aberrations appeared to be inherited from an unaffected parent: dup(3)(q29), del(6)(q12), dup(16)(p13.11). Six aberrations appeared to be inherited from a parental carrier: del(1)(p36.33) joined with dup(12)(q24.32), del(21)(q22.2q22.3) joined with dup(11)(q24.2q25), del(X)(q22.3) and del(1)(q21.1). In two cases, parents were not available for testing: del(17)(q11.2q12) and del(2)(q24.3q31.1). Our results show that the use of oligonucleotide-based array- CGH in a clinical diagnostic laboratory increases the detection rate of pathogenic submicroscopic chromosomal aberrations in patients with mental retardation and congenital abnormalities, but it also presents challenges for clinical interpretation of the results (i.e., distinguishing between pathogenic and benign variants). Difficulties with analysis notwithstanding, the array-CGH is shown to be a sensitive, fast and reliable method for genome-wide screening of chromosomal aberrations in patients with mental retardation and congenital abnormalities.
亚微观结构染色体畸变（微重复和微缺失）被认为是智力迟钝的常见原因。这些所谓的拷贝数变异现在可以使用各种基于阵列的比较基因组杂交（array-CGH）平台进行常规检测，这些平台能够在全基因组范围内识别致病性基因组失衡。在本研究中，基于寡核苷酸的array-CGH被用于研究一组23例智力迟钝、发育迟缓、畸形特征或先天性异常的患者。Array-CGH在总共12例患者中确认或发现了16种染色体畸变。对亲本样本的分析表明，有5种畸变是新发的：del(1)(p36.33p36.23)、del(4)(p16.3p16.2)合并dup(8)(p23.3p23.1)、del(6)(q14.1q15)、del(11)(q13.1q13.4)。3种畸变似乎是从未受影响的亲本遗传而来：dup(3)(q29)、del(6)(q12)、dup(16)(p13.11)。6种畸变似乎是从携带异常的亲本遗传而来：del(1)(p36.33)合并dup(12)(q24.32)、del(21)(q22.2q22.3)合并dup(11)(q24.2q25)、del(X)(q22.3)和del(1)(q21.1)。在2例中，无法获得亲本样本进行检测：del(17)(q11.2q12)和del(2)(q24.3q31.1)。我们的结果表明，在临床诊断实验室中使用基于寡核苷酸的array-CGH可提高智力迟钝和先天性异常患者致病性亚微观染色体畸变的检出率，但这也给结果的临床解释带来了挑战（即区分致病性和良性变异）。尽管分析存在困难，但array-CGH被证明是一种用于智力迟钝和先天性异常患者全基因组染色体畸变筛查的灵敏、快速且可靠的方法。
