Genetic testing involves examining a person’s biological material to identify changes in genes, chromosomes, or proteins. These tests can help confirm or rule out a suspected genetic condition, or assess an individual’s risk of developing or passing on a genetic disorder. Chromosomal microarray (CMA) testing is a specific type of genetic test used to identify particular genetic changes. It plays a significant role in detecting genetic variations that might be linked to developmental or health concerns.
Understanding CMA Genetic Testing
CMA stands for chromosomal microarray, a diagnostic tool identifying genetic causes of developmental problems or illness. It is typically performed for unexplained developmental delays, intellectual disabilities, or congenital anomalies, or in prenatal diagnosis when other tests are inconclusive. CMA works by identifying small segments of missing or extra DNA, known as copy number variants (CNVs). This method offers higher resolution than older techniques like karyotyping, detecting submicroscopic changes too small for traditional microscopy.
How CMA Testing Works
The process of CMA testing begins with sample collection, commonly involving a blood sample, but amniotic fluid or chorionic villus samples can also be used. Once collected, the patient’s DNA is extracted and prepared for analysis on a specialized “microarray chip.” This chip contains thousands of known DNA sequences, called probes, which correspond to specific regions across the human genome.
The core concept involves comparing the patient’s DNA to a reference DNA sample, typically from a healthy individual. The patient’s DNA and the reference DNA are labeled with different fluorescent dyes and then applied to the microarray chip. The labeled DNA fragments bind to their complementary probes on the chip. A scanner then measures the intensity of the fluorescent signals, indicating the amount of DNA present at each probe location. Differences in signal intensity reveal gains (duplications) or losses (deletions) of genetic material in the patient’s sample compared to the reference.
Genetic Conditions Detected by CMA
These changes in the amount of DNA can lead to various genetic conditions. For instance, CMA can identify the genetic changes associated with DiGeorge syndrome, characterized by a specific microdeletion on chromosome 22. It also helps in diagnosing conditions like Prader-Willi syndrome or Angelman syndrome, which involve deletions on chromosome 15.
The test is also a first-tier diagnostic tool for individuals with unexplained developmental delay, intellectual disability, or autism spectrum disorder. CMA identifies genetic abnormalities in many patients with autism spectrum disorders. Detecting these CNVs is important for diagnosis and guiding management strategies.
Interpreting CMA Test Results
CMA test results generally fall into three main categories. A “normal” or “negative” result indicates no significant copy number variants were detected, meaning the tested chromosomal segments have the expected amount of DNA.
A “pathogenic” or “abnormal” result signifies the detection of a known disease-causing CNV, providing a genetic diagnosis. The third category is a “variant of uncertain significance” (VUS), meaning a CNV was found but its clinical impact is not fully understood. VUS results can occur because the identified CNV might be new, or there might not be enough scientific data to definitively link it to a disease. Genetic counseling is important for interpreting these results and understanding their implications for the individual and their family.
What CMA Cannot Detect
While CMA is a powerful diagnostic tool, it has limitations in the types of genetic changes it can detect. CMA cannot identify single gene mutations, which are changes within a single gene’s DNA sequence. Conditions like cystic fibrosis or sickle cell anemia, caused by these small, specific changes, require different genetic tests, such as gene sequencing.
The test also does not detect balanced rearrangements, where chromosomal material is rearranged but no net gain or loss of DNA occurs. These include balanced translocations or inversions, which may require traditional karyotyping. Furthermore, CMA may not detect very small changes below its resolution or low-level mosaicism, where a genetic change is present in only a small percentage of cells. A normal CMA result does not rule out all genetic conditions or other potential causes for a patient’s symptoms.