Patients with an unclear dysmorphia and retardation syndrome
Array-CGH
General Information
Since the introduction of chromosome banding techniques, genome resolution has seen only minor improvements. Even Florescence in situ Hybridisation (FISH) techniques such as Multiplex- FISH and chromosome-based comparative genomic hybridisation (CGH) contributed little to high resolution representations of the entire genome. Chromosome mutations, smaller than 5 megabases (Mb), were not detectable with these methods.
This changed considerably with the advent of a new technique that combined comparative genomic hybridisation and array technology. The simultaneous hybridisation of patient and reference DNA was carried out not on metaphase chromosomes but on a so-called "array" or glass surface. On this "chip" are located several thousand to houndreds of thousands segments of the human genome, immobilised on a grid. If these segments are comprised of oligonukleotides, the technique is referred to as a Oligo-Array-CGH. If these segments are comprised of BAC (bacterial artificial chromosome) clones with human DNA inserts, the technique is referred to as a BAC Array-CGH.
Patients with a complex retardation syndrome (dysmorphic stigmata, mental retardation, developmental delays and possible neurological symptoms) are often difficult to assess in terms of known syndromes. With such patients, most often children, the cause is a structural chromosome aberration that can be detected (depending on size) either with a conventional chromosome analysis, an analysis of the chromosomal subtelomer regions or only by means of an Array-CGH. The symptoms are caused by differing degrees of loss or gain of chromosomal material in a particular child and are normally not attributable to a specific syndrome.
This test closes the diagnostic gap between conventional chromosome analysis, FISH diagnostics, and molecular genetic testing.
In up to 20% of cases, children with unclear dysmorphic and retardation syndromes and negative genetic test results have a pathologic Array-CGH test.
Diagnostic
Indication
Method
An Array-CGH is comparative genomic hybridisation (CGH) on a glass surface (or "chip") on which specific oligonucleotides are fixed. The even distribution is referred to as an "array". The arrays used are that of BlueGnome (Agilent 180K Agilent ISCA design). The analysis is carried out using BlueFuse Multi software.
Loss or gain in genomic sequences is detected by means of differing relationships in color intensities between patient and reference DNA.
Prior to performing Array-CGH diagnostics, genetic causes for the disease should be ruled out by means of a conventional karyotypisation or, if appropriate, targeted molecular genetic testing.
Sample Requirement
2 - 4 ml of EDTA-Blood for the Array-CGH analysis
2 - 5 ml of heparinised blood for karyotyping and FISH
Duration
2 - 3 weeks