Professor Ants Kurg, University of Tartu
Professor Katrin Õunap, University of Tartu
Dr. rer. nat. Hartmut Engels, University of Bonn, Germany
The higher-order architecture of the human genome has been shown to predispose to structural rearrangements, including losses and gains of DNA segments. Most rearrangements have no effect on human phenotype. However, changes in specific genomic regions can cause various pathological conditions, such as abnormal mental and physical development, neurological disorders, cancer etc.
Chromosomal microarray analysis (CMA) is a novel chromosome analysis method that offers the capacity to examine the entire human genome in a single experiment to detect changes in chromosome number and structure. Compared to conventional chromosomal analysis - G-banding - the resolution of CMA is at least 10-20-fold higher, which provides a higher diagnostic yield. In general, CMA is able to detect chromosomal abnormalities in 15-20% of patients with developmental problems and/or intellectual disability.
Since 2011, CMA is on the official service list of the Estonian Health Insurance Fund and is performed as the first-tier cytogenetic diagnostic test for patients with 1) developmental delay/intellectual disability, 2) autism spectrum disorders, and/or 3) multiple congenital anomalies. CMA can also be performed in some prenatal cases. However, in Estonia, G-banding remains the primary cytogenetic test in prenatal diagnostics. Detection of pathogenic aberration by CMA excludes further expensive analyses. In case of a normal result, in further diagnostic procedures it is reasonable to concentrate on rare monogenic disorders and metabolic diseases.
This study summarizes the Estonian experience of using CMA in routine clinical practice. The critical step, especially in prenatal diagnostics, is interpretation of CMA findings, which can be quite difficult in some cases. Close collaboration between cytogeneticists and clinical geneticists is important in terms of interpretation and providing proper genetic counseling. In addition, it should be kept in mind that the interpretation of CMA findings is based on current knowledge and may evolve over time. Therefore, it is important to re-evaluate CMA results over the time.