Molecular karyotype (aCGH) using high resolution analysis (≥50-100 Kb)

Molecular karyotype (arrayCGH-aCGH) has brought about revolutionary changes in clinical cytogenetics and today is the undisputed reference method for the diagnosis of many genomic diseases (mental retardation, developmental delay, congenital malformations, etc.) associated with chromosomal imbalances, also known as Copy Number Variations – CNV’s.

This level of aCGH is applied when the clinical data require detailed analysis of chromosomal imbalances, which may be the cause of the observed clinical symptoms in the patient. This test is internationally recommended as first-line test in patients with mental disability and developmental disorders. Specifically, it is typically applied in patients with an abnormal phenotype, which may include mental retardation with or without constitutive abnormalities, developmental delay, autism, learning problems, etc

It is an extremely powerful tool for the diagnosis of the underlying genetic cause of many pathological phenotypes, which are not revealed through conventional karyotype analysis. It is also a valuable test for the clinical geneticist in order to provide detailed genetic counseling, by assessing both the severity of the genetic defect and the likelihood of recurrence in the family. Detailed genetic counseling is recommended both before and after performing the test.

InterGenetics began the clinical application of this test routinely in 2007 and has gradually developed an internal database of Greek patients, incorporating also all findings from >25,000 cases from international databases which have been investigated by molecular karyotype-aCGH. This database is constantly updated with new findings and data. This allows us as a most reliable clinical evaluation of the findings in each patient tested.

We apply the proven and validated for clinical applications 2x105K microarray CGH, covering the human genome at an analytical level of 50-100 Κb. The test is typically performed from a peripheral blood DNA sample and requires 3-4 weeks, although the time depends on each case and the clinical parameters. In selected cases and depending on the nature of the findings, testing of the parents may be required before the final evaluation.

The test is highly sensitive and complex. Therefore, the analysis and the clinical evaluation of the results should be performed by a highly skilled group of clinical and molecular geneticists, ensuring the maximum diagnostic validity for the patient and the family.

Proper clinical genetic assessment and genetic counseling, both before and after testing, is essential in order to determine the optimum testing strategy and also to communicate properly the concepts of pathological and normal.

The method reveals only imbalances (quantitative changes) of genetic material. It is therefore not able to detect balanced rearrangements / translocations or rearrangements/translocations with imbalances of size <50 – 100 Kb.

Furthermore, aCGH analysis may not detect all types of chromosomal mosaicism occurring at <10-15% of cells, which in any case are usually non-pathogenic. Finally, it is obvious that the method does not detect point mutations in DNA, associated with gene disorders such as thalassemia, cystic fibrosis, etc.