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:
Deletions and duplications of chromosome segments, also known as Copy Number Variations (CNVs) are one of the genetic causes of congenital developmental diseases of the central nervous system with complex inheritance. There is a high comorbidity of diseases such as epilepsy, autism, neuropsychological delay, intellectual disability (ID). For example, 70% of patients with autism also develop ID. Between 15-35% of children with epilepsy have autistic stigmas and vice versa - epilepsy occurs in up to 46% of patients with autism, and is more common in those with comorbid ID. In about 20% of cases of ID, epileptic seizures are also observed. Microdeletions / duplications underlie the pathogenesis of some neuropsychiatric phenotypes such as ID / developmental delay, autism, epilepsy and schizophrenia. For example, deletions in 16p11.2 as well as duplications in 16p13.3 and 15q11q13 regions are associated with both autism and epilepsy. Epilepsy, autism and intellectual disability are comorbid symptoms of Down syndrome and other complex microdeletion / duplication syndromes. Microarray technologies applies the 'genotype first' approach, after which these diseases are defined on the basis of detected and associated CNVs, thus enabling a more accurate and rapid diagnosis in the affected patients.
Reasons for reffering:
Patients with unclear developmental delay, nervous system dysfunction, intellectual disability, neuropsychological retardation, congenital anomalies affecting one or several organs and / or systems, and dysmorphisms (general and facial).
Interpetation of the results:
The detection of pathogenic copy variants, such as deletions and/or duplications by this method will reveal the genetic cause of a specific neuropsychiatric disorders (epileptic seizures, ID, motor and behavioral disorders) with or without general or facial dysmorphisms, and will help make am accurate 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 4x180K, ISCA v2
The method involves screening the entire genome in a single experiment to look for microdeletion / duplication changes affecting one or more chromosomes. The 4x180K platform analyzes a portion of the genome covering approximately 180 Kb of DNA, making the method with higher resolution than standard cytogenetic techniques.
SurePrint G3 Unrestricted CGH 4x180K, ISCA v2: the platform contains immobilized 180,000 60-mer oligonucleotide samples, with a sample density of 13 Kb (11 Kb in areas with Ref Seq genes) with greater coverage in areas containing known genes, promoter and telomeric regions.
Sensitivity of the method: 99%
What does the test involve?
Isolation and storage of isolated DNA 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: Venous blood or DNA
For more information, please read "Biological Sample Requirements and Transport Information" carefully.
