Inheritance of subtelomere rearrangements
When a child carries a telomere rearrangement there is approximately a 50% chance the child has inherited the abnormality from one of the parents. Because of this significant risk, we recommend all parents of children with telomere abnormalities to undergo targeted telomere analysis. In some cases the parent carries a balanced translocation. A balanced translocation involves the exchange of pieces between two chromosomes. All of the genetic material is present, but in the wrong location. Carriers of balanced translocations are usually normal and are not clinically affected. The figure below is a FISH image showing a carrier of a balanced translocation between the long arm of chromosome 2 and the short arm of chromosome 17. This individual still has two copies of the 2q telomere probe (shown in red) but one of the copies is located on chromosome 17 (called a derivative, or der(17)) instead of chromosome 2. Likewise, this individual still has two copies of the 17p telomere probe (shown in green), but one of the copies is on chromosome 2 (called a derivative, or der(2)) instead of chromosome 17.
However, carriers of balanced translocations can pass unbalanced translocations on to their offspring. An unbalanced translocation results in the loss of a chromosome segment and a gain of another chromosome segment.
When a parent carries a balanced form of a translocation, there are several different combinations that can be passed on to his or her children:
normal individual with a normal set of chromosomes,
normal individual with the balanced form of the rearrangement just like the parents,
and two different forms of the unbalanced translocation.
The image below shows one of the children of the balanced translocation carrier whose FISH results are shown in the image above. The child inherited an unbalanced form of the translocation. As shown in the image, there are not two copies of each green and red probe in this individual: there are three green probe signals present and only one red probe signal. Therefore, this indivdual inherited a normal chromosome 2 and normal chromosome 17 from one parent and inherited a normal 17 and a derivative chromosome 2 from the parent who carries the balanced translocation. This inheritance pattern results in monosomy (one copy) of the 2q telomere region and trisomy for the 17p telomere region.
A carrier of an unbalanced translocation has up to a 50% chance of having an abnormal pregnancy outcome (miscarriage or abnormal child). Some unbalanced translocations are not compatible with life and result in miscarriage.
Another reason for testing parents of children with subtelomere abnormalities is to rule out the possibility of a benign variant. A benign variant is a change that does not result in any clinical abnormalities and likely represents a normal variation in the population. One of the steps in determining if an abnormality is a benign polymorphism is to study the parents. If a normal parent carries the identical rearrangement as the affected child, the rearrangement is more likely to be a benign variant and not the cause of the child's clinical features.