Copy Number + SNP
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ACMG Practice Guidelines on Microarray Testing
The American College of Medical Genetics (ACMG) published practice guidelines on microarray testing in September 2010. Their first recommendation states:
- Cytogenetic microarray (CMA) testing for copy number
variation (CNV) is recommended as a first-line test in
the initial postnatal evaluation of individuals with the
- Multiple anomalies not specific to a well-delineated genetic syndrome
- Apparently nonsyndromic developmental delay/ intellectual disability
- Autism spectrum disorders
A copy number + single nucleotide polymorphism (SNP) chromosomal microarray test is now available from Mayo Medical Laboratories.
To help clients gain a better understanding of this new test, we have compiled the following FAQs.
Frequently Asked Questions
What are the advantages of a CMA copy number + SNP test?
This CMA test utilizes >1.9 million copy number probes and approximately 750,000 SNP probes for the detection of copy number changes and regions of excessive homozygosity.
Identification of regions of excessive homozygosity on a single chromosome could suggest uniparental disomy (UPD), which may warrant further clinical investigation when observed on chromosomes with known imprinting disorders associated with UPD. In addition, the detection of excessive homozygosity on multiple chromosomes may suggest consanguinity and therefore could be useful in determining candidate genes for further testing for autosomal recessive disorders.
Should I be aware of any cautions when offering this test to patients?
When counseling patients regarding the CMA copy number + SNP it is appropriate to discuss the potential for incidental findings or findings that may not be related to the patient’s clinical presentation, such as adult-onset conditions.
In addition, since the CMA copy number + SNP has the ability to detect consanguinity, patients may benefit from being informed of this possibility prior to testing. While the CMA copy number + SNP has the capability of detecting uniparental disomy, it is important to note that it is only diagnostic for isodisomy (the presence of 2 identical homologous chromosomes transmitted from only 1 parent).
In some cases, excess homozygosity may be suggestive of heterodisomy (the presence of two different homologous chromosomes transmitted from only one parent); however, additional UPD testing requiring parental samples is necessary to confirm heterodisomy. Furthermore, while UPD can be detected by the CMA copy number + SNP, the parent of origin is not discernible.
Similar to the copy number-only CMA, the CMA copy number + SNP cannot detect balanced rearrangements and may not be capable of detecting low-level mosaicism. It also does not detect point mutations, small deletions or insertions below the resolution of this assay, or other types of mutations such as epigenetic changes. Finally, test results are sometimes of uncertain clinical significance, and studies of additional family members may be required to assist with interpretation.
Who should I call if I have questions about ordering this test or interpretation of patient results?
Please call the genetic counselor on-call number at 800-533-1710, extension 8-2952, with any questions. Genetic counselors are available Monday through Friday from 8 am to 5 pm CST.