What is a terminal deletion?
A terminal deletion is a cytogenetic abnormality involving the loss of a segment of DNA from the end (terminus) of a chromosome. It can result from various mechanisms, including unequal meiotic crossovers, chromosomal breaks, and deletions. Terminal deletions can range in size from small, involving only a few genes, to large deletions that encompass entire gene clusters or even chromosomal bands.
The clinical consequences of terminal deletions vary depending on the location and extent of the deleted region. Some terminal deletions may result in mild or no phenotypic effects if the deleted region does not contain essential genes. However, deletions of critical genes can cause various developmental disorders, malformation syndromes, intellectual disabilities, or other health problems.
Terminal deletions can be detected through cytogenetic analysis, such as karyotyping or fluorescence in situ hybridization (FISH). Molecular techniques like array-based comparative genomic hybridization (aCGH) or whole-exome sequencing (WES) can also be used to identify and characterize terminal deletions.
Examples of well-known terminal deletion disorders include:
1. Cri du Chat syndrome: Caused by a terminal deletion of the short arm of chromosome 5 (5p). It is characterized by a distinctive high-pitched cat-like cry, intellectual disability, developmental delays, and distinctive facial features.
2. Wolf-Hirschhorn syndrome: Resulting from a terminal deletion of the short arm of chromosome 4 (4p). It is associated with growth retardation, intellectual disability, seizures, and distinct craniofacial features.
3. DiGeorge syndrome: Involves a terminal deletion of the long arm of chromosome 22 (22q11.2). It is characterized by congenital heart defects, immunodeficiency, and developmental delays.
Terminal deletions can also occur as acquired genetic alterations in somatic cells, contributing to the development of certain types of cancer. In such cases, the deleted region may harbor tumor suppressor genes that, when lost, allow uncontrolled cell growth and contribute to cancer progression.
Studying and understanding terminal deletions are essential in clinical genetics as they provide insights into the genetic basis of developmental disorders and help guide genetic counseling and medical management for individuals carrying these chromosomal abnormalities.