Deletion screening is a specialized type of genetic testing that identifies missing pieces of genetic material, known as deletions, within an individual’s DNA. These tests analyze a person’s chromosomes or specific genes. The information gained can offer insights into various health conditions, from developmental delays to inherited disorders. This analysis serves as a tool for understanding potential genetic causes behind health concerns or for assessing risks in family planning.
What Are Genetic Deletions?
Genetic deletions occur when a segment of DNA is lost from a chromosome. This loss can range in size from a single nucleotide, a basic building block of DNA, to large sections encompassing multiple genes or even an entire chromosome piece. Chromosomes are structures within cells that contain DNA and genes, which carry instructions for how the body develops and functions.
Even small deletions can significantly impact health, as the missing genetic material may contain genes responsible for proper bodily function. For instance, a deletion not divisible by three nucleotides can cause a “frameshift,” altering how the genetic code is read and potentially leading to a non-functional protein. These deletions can arise from errors during DNA replication or chromosomal crossover during cell division, or they can be induced by external factors like heat, viruses, radiation, or certain chemicals.
How Deletion Screening Works
Deletion screening involves collecting a biological sample and analyzing its DNA in a laboratory. Blood samples are commonly used, providing a rich source of genetic material. For prenatal screening, amniotic fluid or chorionic villus samples may be collected to analyze fetal DNA. A buccal smear, collecting cells from the inside of the cheek with a cotton swab, can also be performed.
Once the sample arrives at the laboratory, DNA is extracted and prepared for analysis. Techniques like chromosomal microarray (CMA) are frequently employed to detect copy number variations, including deletions, across the genome. Fluorescence In Situ Hybridization (FISH) is another method that uses fluorescent probes to “paint” specific chromosomes or parts of chromosomes, helping to identify large deletions or other chromosomal abnormalities. Specific gene panel sequencing or targeted deletion/duplication analysis by comparative genomic hybridization (CGH) can also detect smaller deletions within particular genes, which might be missed by other methods.
Conditions Identified by Deletion Screening
Deletion screening can identify a range of genetic conditions and developmental issues linked to missing genetic material. For example, Cri du chat syndrome, characterized by a high-pitched, cat-like cry in infants, results from a deletion on chromosome 5. Individuals with this syndrome often experience intellectual disability, developmental delays, and distinct facial features.
Wolf-Hirschhorn syndrome is associated with a deletion on chromosome 4 and presents with unique facial features and delayed physical growth. DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is caused by a deletion on chromosome 22 and can lead to immune system problems, heart defects, and abnormalities of the face and neck. Prader-Willi syndrome and Angelman syndrome are both linked to deletions on chromosome 15, but their specific presentation depends on whether the deletion is inherited from the father or mother. These conditions often involve challenges such as insatiable appetite and childhood obesity in Prader-Willi, or developmental delays and speech difficulties in Angelman syndrome.
When Deletion Screening is Considered
Deletion screening is considered in specific clinical scenarios to help diagnose or assess the risk of genetic conditions. For prenatal screening, it may be recommended if ultrasound findings suggest fetal abnormalities, or if there is advanced maternal age, which is associated with a higher risk of chromosomal changes. Non-invasive prenatal testing (NIPT), which analyzes cell-free DNA from a maternal blood sample, can screen for certain deletions, though positive NIPT results typically require confirmatory diagnostic testing.
Following birth, deletion screening may be considered for postnatal diagnosis in individuals with unexplained developmental delays, intellectual disabilities, or multiple congenital anomalies. If a child presents with medical problems suggesting a deletion syndrome, such as heart problems linked to 22q11.2 deletion syndrome, the test would likely be ordered. Carrier screening may also be performed for individuals or couples with a family history of a known deletion syndrome to assess their risk of passing the condition to their children.
Understanding Your Deletion Screening Results
Understanding deletion screening results involves interpreting various classifications. A “positive” result means a genetic deletion or variant was detected. This indicates a missing segment of DNA, likely the cause of or contributing to a specific genetic condition. A “negative” result indicates no known deletion was found, suggesting the absence of the specific genetic change being screened for.
Sometimes, results may be “inconclusive” or classified as a “variant of uncertain significance.” This means a genetic change was identified, but there is not enough scientific evidence to definitively classify it as harmful or benign. Genetic counseling is recommended to help individuals and families interpret these complex results, understand their implications, and discuss potential next steps. These steps might include confirmatory testing, specialized medical management, or discussions about family planning.