Abstract
Microarray-based comparative genomic hybridization (array CGH) is a newly emerged molecular cytogenetic technique for rapid evaluation of the entire genome with sub-megabase resolution. It allows for the comprehensive investigation of thousands and millions of genomic loci at once and therefore enables the efficient detection of DNA copy number variations (a.k.a, cryptic genomic imbalances). The development and the clinical application of array CGH have revolutionized the diagnostic process in patients and has provided a clue to many unidentified or unexplained diseases which are suspected to have a genetic cause. In this paper, we present three clinical cases in both prenatal and postnatal settings. Among all, array CGH played a major discovery role to reveal the cryptic and/or complex nature of chromosome arrangements. By identifying the genetic causes responsible for the clinical observation in patients, array CGH has provided accurate diagnosis and appropriate clinical management in a timely and efficient manner.
Highlights
Genomic disorders, resulting from DNA rearrangements involving region-specific repeat sequences, are caused by abnormal dosage of one or more genes located within the rearranged genomic fragments
Array CGH is able to uncover numerous copy number variations (CNVs) of not-yet-known clinical significance scattered throughout the human genome
The copy number variations identified by a CGH, which we considered for further validation, were analyzed using fluorescence in situ hybridization (FISH) analysis
Summary
Genomic disorders, resulting from DNA rearrangements involving region-specific repeat sequences, are caused by abnormal dosage of one or more genes located within the rearranged genomic fragments. Cytogenetic analysis has been a useful diagnostic tool for this disease category especially in idiopathic developmental delay/mental retardation, multiple congenital anomalies, dysmorphism, and pregnancy at risk for chromosomal abnormalities. The limitation of band resolution in the conventional cytogenetic methodology karyotype (5–10 Mb) has prompted the development of technologies which can identify previously unrecognized chromosomal anomalies. The array CGH platforms used for clinical diagnosis are able to detect nonmosaic and mosaic aneuploidies, subtelomeric imbalances, known microdeletion/microduplication syndromes, and other unique unbalanced chromosomal rearrangements [2,3,4]. The detection rate has been improved to 10–16% in patients with a normal karyotype [5, 6]. Array CGH is able to uncover numerous copy number variations (CNVs) of not-yet-known clinical significance scattered throughout the human genome
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