Genetic effects of chromosome deletion

As we all know, many diseases are genetic. Therefore, many mothers will be very worried when they are pregnant. Genetics has a lot to do with chromosomal deletions in our body's genes. Perhaps many people do not care about the genetic effects of chromosome deletion and do not understand it, but it will be reflected in the body in each generation of inheritance.

There are two types of chromosome deletions. One is the deletion of the entire chromosome, such as 21-monosomy, 18-monosomy, 13-monosomy, etc., which is common in aborted embryos; the other is the deletion of chromosome fragments, that is, only a part of the chromosome is missing. Such deletions can be pathogenic, but they can also be benign.

What is the mechanism of chromosome deletion?

1. The loss of an entire chromosome is generally caused by nondisjunction of chromosomes during the formation of gametes (sperm and eggs). The figure below shows three types of gametes, namely type n (normal gametes), type n-1 (missing a chromosome) and type n+1 (an extra chromosome). When n-1 gametes are fertilized with normal gametes, 2n-1 embryos are formed, which have one less chromosome than normal embryos. Because one chromosome is missing, many genes are missing. For example, if there are more than 300 genes on chromosome 21, then the lack of one chromosome 21 is equivalent to the lack of more than 300 genes. Generally speaking, without so many genes, it is impossible for the embryo to grow and develop normally, so it will usually miscarry in the early stages of pregnancy. It can also be seen from the above figure that the ratio of n-1 type and n+1 type gametes is equal, which means that the frequency of occurrence of trisomy and monosomy is equal. For example, the ratio of trisomy 21 and monosomy 21 is the same, but trisomy 21 can be born, while monosomy 21 is aborted. Therefore, the cause of miscarriage should first be considered as the lack of a chromosome in the embryo.

2. Chromosome fragment loss is generally caused by ionizing radiation from various rays such as α, β, γ and x, which causes chromosome breakage and subsequent fragment loss. Since the missing fragments are often not large, the missing genes are not many, and most embryos can grow and develop. The common cat cry syndrome in clinical practice is the deletion of a fragment on the short arm of chromosome 5 (see the figure below), which is named because the child has a cat-like crying sound.

Clinical manifestations of chromosome deletion:

1. The deletion of a whole chromosome usually leads to miscarriage in early pregnancy.

2. The deletion of chromosome fragments generally leads to three major clinical manifestations, namely intellectual developmental disorders, overall developmental delay and multiple malformations. It can also lead to epilepsy, obesity, delayed language development and autism.

Genetic counseling for chromosome segment deletion:

The deletion of a chromosome segment may or may not cause disease. The reason may be related to the number and importance of genes involved in the deletion. In addition, mechanisms such as recessive carriage, incomplete penetrance, and gene imprinting effects can also cause individuals to present a normal phenotype. During consultation, it is usually recommended to first do a family deletion test. If healthy family members also have the same deletion, it is very likely that the deletion is benign. International genetic databases are then searched for matching or similar individuals with the deletion to aid in diagnosis. Generally speaking, it is rare to find an individual with exactly the same deletion in the database, so it is often very difficult to determine the pathogenicity of chromosomal deletions, and sometimes a comprehensive assessment must be made based on clinical manifestations such as fetal B-ultrasound results. I recently consulted a pregnant mother whose fetus had the same chromosome 10 deletion as hers (see the picture below), but no abnormalities were found in the fetal B-ultrasound test, indicating that the deletion is likely to be benign.