A chromosomal microarray (CMA) is used to detect small genomic changes. The CMA provides a genome-wide analysis of DNA copy number changes, with targeted probe coverage in disease-associated regions. It detects microduplications and microdeletions around 100 times smaller than those seen by conventional G-band chromosome analysis (karyotype). The inclusion of single nucleotide polymorphism (SNP) probes in the microarray design enables the detection of large regions of homozygosity, which can indicate uniparental disomy or recessive disease.
This test does not detect sequence-based changes, fragile X, low level mosaicism, or balanced chromosome rearrangements.
Indications for testing:
1. One or more structural fetal anomalies detected by ultrasound (including IUGR or NT >3.5mm)
2. Structural chromosome imbalance identified by G-band karyotyping
3. Family history of a chromosome rearrangement. Liaison with Genetic Health NZ or this laboratory is recommended to determine the most appropriate investigation
4. On a case by case basis following consultation with a Clinical Geneticist, a Pathologist or Fetal-Maternal Medicine specialist
Genetics - Cytogenetics
Molecular karyotype, prenatal
Amniotic fluid (AF): at least 18mL of clear fluid from 16 weeks gestation onwards, at ambient temperature. DNA is usually extracted from whole fresh fluid. Rapid aneuploidy screening by QF-PCR or FISH is performed prior to the CMA. Back-up cultures are also established. If possible, send parental bloods together with the prenatal specimen to avoid a delayed result. 3mL of EDTA (purple top) and 3mL of lithium heparin (green top) from each parent, well mixed and at ambient temperature, is required.
Limitations: blood-stained AFs, small or acellular samples or those with gestation greater than 20 week) are cultured prior to DNA extraction to optimise DNA quality and results. This may delay results by up to two weeks.
Chorionic villus sample (CVS): 15mg of clean villus material, from 11 weeks gestation onwards, collected in RPMI Tissue Transport Medium in a universal container. DNA is usually extracted from whole fresh tissue. Rapid aneuploidy screening and back-up cultures are performed. If possible, send parental bloods together with the prenatal specimen to avoid a delayed result. 3mL of EDTA (purple top) and 3mL of lithium heparin (green top) from each parent, well mixed and at ambient temperature, is required.
Limitations: small samples (less than 10mg) will be cultured prior to DNA extraction in order to obtain sufficient cells. This may delay results by up to two weeks.
Fetal PM tissue or Products of conception (POC): at least 15mg of each tissue collected in RPMI Tissue Transport Medium in a universal container. Aneuploidy screening by QF-PCR or FISH is performed prior to the CMA.
POCs: please also send a maternal blood (2ml EDTA purple top) together with the sample for maternal cell exclusion testing. A paternal specimen is only occasionally required and will be requested if required.
Limitations: samples unsuitable for CMA testing include:- POC with no clearly identifiable villus tissue; POC with significant maternal cell contamination; poorly degraded DNA; low yield DNA
To order RPMI Tissue Transport Medium
Phone CHL Patient and Client Services 03 364 0484 between 09.00-17.00, Mon-Fri and allow at least one working day for delivery. In emergency the specimen can be collected into sterile saline.
Ambient (8 - 24 degrees Celsius)
Same day or overnight by courier
The clinical significance of any copy number change identified during CMA analysis is assessed by interrogation of multiple databases and current literature, association between patient phenotype and gene content/function of the affected region(s) or suspected syndrome. Interpretation is based on current knowledge at the time of assessment.
Results are reported as:
1. No clinically relevant copy number change
2. Copy number change of uncertain or unknown significance
3. Clinically significant copy number change
4. Clinically significant homozygosity, indicative of UPD
CMA uses a Perkin Elmer designed 180k CGX SNP-HD, manufactured by Agilent with 110,000 copy number probes and 60,000 SNP probes. Genome build hg19. This is a targeted array with genomic coverage which includes over 245 syndromes, at least 980 functionally significant genes and subtelomeric and pericentric regions. Copy number resolution: approximately 160kb (backbone) and 40kb at clinically significant regions. SNP resolution: regions of homozygosity greater than 5MB.
Analysis Software: Cytogenomics (Agilent) and Genoglyphix (Perkin Elmer)
Method: patient DNA and a reference DNA are labelled with different fluorescent dyes. Both the reference DNA and patient DNA are hybridised overnight to probes on the array. The array slide is scanned to compare fluorescence at each DNA probe. Gains and losses of genomic material are detected by a change in fluorescence intensity ratio between the patient and the reference. A duplication is indicated by a Log2 ratio of close to 0.58, while a deletion is indicated by a log 2 ratio close to -1. Gains and losses are then assessed for potential clinical significance.
$1008.06 (Exclusive of GST)
CMA testing does not detect balanced rearrangements and very small imbalances including sequence-based changes, regions of homozygosity less than 5Mb. It may not detect mosaicism under 20% or some cases of uniparental disomy. The effective screening resolution is approximately 50 kb in known clinically significant regions and 200kb elsewhere in the genome.
Copy number changes of uncertain or unknown significance are reported after consultation with a genetic pathologist or Genetic Health NZ. Copy number changes that are considered benign or likely benign are not reported. Regions of homozygosity totalling <3% of the genome are not routinely reported. Further detailed analysis of regions of homozygosity can be performed on request if a specific recessive disorder is suspected. A list of all unreported findings is available on request.
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