Chromosomal Microarray (Prenatal)
According to ACMG Microarray methodologies, including array comparative genomic hybridization and SNP detecting arrays, are accepted as an appropriate first-tier test for the evaluation of imbalances associated with intellectual disability, autism, and multiple congenital anomalies1
Chromosomal microarray (CMA) is a sophisticated microarray technology that analyzes the entire genome, detecting submicroscopic chromosomal deletions/duplications known as copy number variants (CNVs). CNVs are commonly associated with various genetic disorders that are often missed by traditional karyotyping. This high-resolution, whole-genome technique is rapidly replacing traditional karyotyping as the primary genetic test for screening suspected chromosomal anomalies. CNVs are linked to a diverse range of genetic disorders, including Autism Spectrum Disorders, autosomal disorders, X-linked Inheritance, UPD (Uniparental Disomy), and more.
- Clinical diagnosis of cytogenetic abnormalities.
- Differentiation between de novo(new unexplained mutations) and familial history of disorders
- Prenatal diagnosis of at-risk pregnancies & at-risk family members.
- To clarify the clinical significance of copy number changes
- To influence the management of the conditions/disorders in a better way including lifestyle interventions.
When is it recommended
Diagnosis for fetal chromosomal imbalances is important as it is the contributing factor for some adverse obstetric outcomes - pregnancy loss, genetic syndromes etc. The accurate diagnosis of such chromosomal imbalances is a critical component of prenatal genetic evaluation.
- CMA is recommended for patients undergoing invasive prenatal diagnosis with one or more major fetal structural abnormalities identified by ultrasonographic examination.
- Abnormal maternal serum screen - improved detection of causative abnormalities.
- Advanced maternal age.
- Family history of genetic diseases.
- Consanguine marriages.
CMA is the first step to get the diagnosis you need for the effective management of genetic conditions and their risk of recurrence.
Mapmygenome - CMA Offerings
- Chromosomal Microarray genotyping with Illumina 750K Bead chip optimized for efficient cytogenetic analysis.
- 750000 markers covering ~9000 genes analyzed with emphasis on ~447 disease-associated genes.
- Copy neutral loss of heterozygosity (Cn-LOH) region detected based on intensity & SNP genotype in order to screen for UPD (Uniparental Disomy) & autosomal recessive disorders.
- Copy Number Variations as small as 2.3kB CNV regions detected.
- High-density screening of 324 known cytogenetic regions commonly screened & used as hotspots for cytogenetic testing.
- 495268 genomic structural variants researched from Database of Genomic Variants for better interpretation.
- Also covers: Pericenters and Telomeres | Sex Chromosomes | PseudoAutosomal Region (PAR1 and PAR2) | Common Regions of Interest Associated with Known Syndromes
Comparing all the techniques in prenatal testing
|Increased resolution (~50-100 kb) in CMA allows for Identification of chromosomal imbalances||Resolution limited to around 5 Mb.||Can only detect deletions/duplications of regions specifically targeted by the probe|
|Greater accuracy||Greater chance of missing subtle abnormalities||Rare very small deletions can not be detected.|
|Diagnostic yield ~30%||5 – 10% of diagnostic yield||5 – 10% of diagnostic yield|
|Covers the Whole Genome to detect CNVs||Covers the Whole Genome with low resolution to detect CNVs||Can only detect deletions/duplications of regions specifically targeted by the probe|
|Technique||Platform||Variant types||TAT||Sample requirements|
|Microarray||Illumina 700K gene chip||CNV||3 -4 weeks||Extracted DNA samples (1µg - 2µg), POC 100-200g in PBS Solution, EDTA Blood (2-3ml) for MCC assay, CVS Sample/Amniotic Fluid/Cultured Cells - Cell Pellet in 1.5mL tube|
- South, S., Lee, C., Lamb, A. et al. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med 15, 901–909 (2013).
Is CMA a diagnostic test or a screening test?
CMA is primarily considered a diagnostic test rather than a screening test. It has a higher resolution and can provide more detailed information about the presence of chromosomal imbalances compared to traditional karyotyping.