Analysis of Chromosomal Aberrations in Patients with Mental Retardation Using the Array-CGH Technique: a Single Czech Centre Experience

被引:0
作者
Zrnova, E. [1 ,2 ]
Vranova, V. [1 ,2 ]
Slamova, I. [1 ,2 ]
Gaillyova, R. [2 ]
Kuglik, P. [1 ,2 ]
机构
[1] Masaryk Univ, Fac Sci, Inst Expt Biol, Dept Genet & Mol Biol, Brno 62500, Czech Republic
[2] Univ Hosp Brno, Dept Med Genet, Integrated Lab Mol Cytogenet, Brno, Czech Republic
关键词
array-CGH; DNA microarray; mental retardation; chromosomal aberrations; COMPARATIVE GENOMIC HYBRIDIZATION; DEPENDENT PROBE AMPLIFICATION; ALPORT-SYNDROME; SUBTELOMERIC REARRANGEMENTS; MIDFACE HYPOPLASIA; DE-NOVO; GENE; DELETION; IMBALANCES; THROMBOCYTOPENIA;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:206 / 215
页数:10
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