Download Chromosome Microarray (CMA) Pre-Test Patient

 Chromosome Microarray (CMA) Pre‐Test Patient Information Division of Laboratory Genetics, Cytogenetics Laboratory What are chromosomes? Chromosomes are the structures in each of the body’s cells made up of the genetic information (DNA) that tells the body how to develop and function. They come in pairs, one from each parent and they are numbered from 1 to 22, except for the sex chromosomes; girls have two Xs (XX) and boys have an X and Y chromosome (XY). Chromosomes are not visible with the naked eye, but if you stain them and magnify them many hundreds of times they are visible under a microscope. By looking at a patient’s chromosomes, called karyotyping, it is possible to see if there are any losses or gains of genetic information (imbalance), or if the chromosome is rearranged in any way. However, because the amount of chromosome material lost or gained may be very small, it may be impossible to see this on karyotype. If you have previously had a karyotype, you may have been told that your chromosomes were normal, but there may still be very small gains or losses that were not found. A new enhanced test for looking at chromosomes is available and is called chromosome microarray analysis. What is Chromosome Microarray Analysis (CMA)? CMA is an advance in technology that allows the detection of chromosome imbalances that are smaller than can be detected by karyotyping. These missing or extra pieces are known as copy number variants (CNV). CMA can identify differences between a patient’s DNA and control DNA. In this way, duplications (gains) or deletions (losses) will be identified, as well as the genes contained in these regions. The CMA technique used in BC utilizes more than 2.6 million small fragments of DNA (probes) which represent the genetic information of all chromosomes. These probes are aligned on a glass slide. The patient’s DNA fragments, labeled with a colored dye, are applied to the glass slide, so that they recognize and stick to the corresponding probe. A computer then reads the relative amount of the patient’s DNA on the slide, and determines whether there are any losses or gains (deletions or duplications). Form: CWCG_REQ_00050 Version: 1.0 Last Updated: 25‐Jun‐15 Page 1 Why perform CMA instead of karyotype? CMA is more sensitive than karyotyping in detecting the underlying cause of an individual’s condition (e.g. developmental delay). Recent studies have shown that ~25% of individuals with unexplained developmental delay or multiple anomalies at birth (congenital anomalies) will have a gain or loss of genetic information. About half of these imbalances will provide an explanation for their condition and the remaining half will not provide a clear explanation for their condition; these are called variants of unknown clinical significance (VUS). What are the possible CMA results? 
Normal. No clinically significant losses or gains detected; the cause of this individual’s health and/or developmental problems remains unexplained. o The CMA report may list benign CNVs. A benign CNV is one that is frequent in unaffected individuals and cannot explain the patient’s underlying condition. Parental follow‐up testing is not required. 
Abnormal. Pathogenic gains and / or losses which explain some or all clinical features observed in the patient. An additional blood sample from the patient and parents may be recommended to investigate the origin of the imbalance. Genetic assessment / counselling will be recommended. 
Unknown Clinical Significance (Inconclusive). The detected gains and / or losses are variants of unknown clinical significance (VUS). Testing of parents may assist in interpretation; thus, parental follow‐up studies may be requested. Genetic assessment / counselling will be recommended. 
Common ancestry or consanguinity. The report could list regions of homozygosity (ROH). These are not abnormal, but may indicate some genetic conditions (recessive diseases, uniparental disomy) that may warrant additional genetic counselling. 
Unexpected finding. Although unlikely, CMA may reveal information beyond the intended purpose of diagnosis (i.e. incidental finding). This may include, but is not limited to, being a Form: CWCG_REQ_00050 Version: 1.0 Last Updated: 25‐Jun‐15 Page 2 carrier (not‐affected) of a recessive genetic disorder, having a higher risk of a disease later in life (pre‐symptomatic disease susceptibility), or cancer predisposition. Genetic assessment / counselling will be recommended. What are the limitations of testing? CMA will usually NOT detect the following abnormalities: 
Chromosome rearrangement without loss or gain of genetic material (e.g. inversions and translocations) 
Imbalances in regions not represented on the array 
Presence of genomic abnormality in only a small proportion of cells (mosaicism) 
Small genomic imbalances that are below the sensitivity of CMA or the level of analysis Many conditions cannot be ruled out on the basis of a normal CMA result. CMA is designed to look only for gains and losses of genetic information; it is not designed to look for other types of very small genetic mutations that may be detected by other tests. For example, in some cases, sequencing of a gene may reveal mutations which are not seen with CMA. How will I be given the results? A clinical report will be sent to your physician, who will explain the results to you; based on the results you may be asked to have more testing done, and may be referred for genetic counselling to further discuss the results. How long do the results take? Results are usually available in 6 to 8 weeks. Testing of newborns with multiple abnormalities is considered a priority and results may be available sooner. Form: CWCG_REQ_00050 Version: 1.0 Last Updated: 25‐Jun‐15 Page 3