Test characteristics:

Microarray technologies are used to search for large chromosomal imbalances such as aneuploidies and unbalanced chromosomal rearrangements throughout the human genome. It offers additional opportunities to detect submicroscopic aberrations, or so called Copy Number Variations (CNVs) that are too small to be detected by standard karyotype G-band chromosome banding techniques. These submicroscopic imbalances are also called microdeletions and microduplications. When these CNVs affect specific genomic regions associated with clinical phenotype, they form syndromic complexes. Chromosomal microarray analysis (CMA) has additional diagnostic value, i.e. is capable to make the actual diagnosis in 12-15% of syndromic cases, in which the karyotype is normal.

Basic characteristic of the clinical phenotype: 

In prenatal diagnosis, chromosomal microarray analysis (CMA), with or without karyotyping, is the method of choice for detecting large chromosomal imbalances such as aneuploidies and smaller unbalanced chromosomal rearrangements. CMA offers additional opportunities to detect submicroscopic imbalances or changes in the number of copies (CNVs) that are too small to be seen in a standard G-band chromosome banding techniques. These submicroscopic imbalances are also called microdeletions and microduplications, which are associated with different microdeletion/duplication syndromes. 

Large meta-analyzes in pregnant women show that syndromic genomic aberrations occur in 0.4-2% of fetuses. In the presence of structural fetal abnormalities detected by ultrasound, chromosomal aberrations are detected in 2-18% of cases of isolated abnormality and in 13-35% of cases of multiple abnormalities. In this cases chromosomal microarray analysis significantly improves their diagnosis. In miscarriages, the frequency of chromosomal aberrations is about 50%.

Reasons for reffering:

CMA in prenatal diagnosis when at least one of the following conditions are present:

• multiple fetal malformations and a normal rapid chromosome aneuploidy test result;

• nuchal translucency (NT) ≥3.5 mm;

• presence of a chromosomal translocation or marker chromosome detected by karyotyping;

• intrauterine fetal retardation or fetal death;

• increased risk for genetic disease calculated by biochemical screening

• presence of chromosomal aberration in previous pregnancies

• family history of a specific genetic disease

Interpetation of the results: 

• The detection of pathogenic microdeletions and / or duplications by this method will reveal the genetic cause of the observed abnormal ultrasound findings, deviations from biochemical screening, as well as will help to make a genetic diagnosis.

• The result includes duplications of clinical significance greater than 150 Kb, as well as smaller deletions affecting genes with functional significance. The analysis also detects non-pathogenic copy number variations (CNVs), which are described in the Database of Genomic Variants database (http://dgv.tcag.ca/dgv/app/ home? Ref = GRCh37 / hg19)

• The method cannot detect low levels mosaicism, epigenetic changes, balanced chromosomal rearrangements (inversions and translocations), small insertions / deletions and point mutations, as well as CNVs with a resolution lower than the capabilities of the platform and microarray used; difficulties in detecting polyploidy.

• The genetic counselor will interpret and answer all questions about your result.

Method: 

Chromosomal Microarray analysis / array Comparative Genomic Hybridization (array CGH) using microarray slides SurePrint G3 Unrestricted CGH 4x44K, ISCA v2

The method involves screening of the entire genome in a single experiment for microdeletion / duplication changes affecting one or more chromosomes. With the 4x44K platform, genomic aberrations of up to 150 Kbp can be detected.

SurePrint G3 Unrestricted CGH 4x44K, ISCA v2: the platform contains immobilized 44,000 60-mer oligonucleotide samples, with a sample density of 25Kb (greater density  in regions with Ref Seq genes) with greater coverage in regions containing known genes, promoter and telomeric regions.

Sensitivity of the method: 95%; depends on the quality and quantity of the input material or DNA sample

What does the test involve?

• Isolation of DNA from a prenatal sample (chorionic villi, amniotic cells, fetal part, umbilical cord, placental villi) and storage of the isolated sample.

• Chromosomal Microarray analysis / array Comparative Genomic Hybridization (array CGH) to detect pathogenic copy number variations.

• Software processing of the microarray slide and data analysis. For each patient, data on specific genomic regions associated with previously known chromosomal diseases are analyzed, as well as in accordance with the guiding diagnosis.

• Forming a written result from the genetic test.

• Diagnostic interpretation of results and genetic counseling.

Biological material: chorionic villi, amniotic cells, fetal part, umbilical cord, placental villi or DNA For more information, please read "Biological Sample Requirements and Transport Information" carefully.