Is genetic mosaicism inherited?

[Anonymous]

Is genetic mosaicism inherited?

[Genetic Counselor]

Genetic mosaicism is generally not inherited from parents. Most cases develop spontaneously after fertilisation because of a genetic change that occurs during early embryonic cell division.

To understand this, it is important to distinguish between inherited genetic changes and post-zygotic genetic changes.

Inherited genetic variants are usually present in the egg or sperm before fertilisation. When these reproductive cells combine, the resulting embryo carries the genetic alteration from the beginning of development.

In contrast, mosaicism usually develops after fertilisation. A genetic change occurs in one of the developing embryonic cells, resulting in a mixture of genetically different cell populations.

For example, if a chromosomal error occurs during an early embryonic cell division, some cells may develop with the normal chromosome number, while others may carry an additional or missing chromosome.

This is why most cases of mosaicism are considered sporadic rather than inherited.

However, there is an important exception.

Gonadal mosaicism, also known as germline mosaicism, occurs when a genetic change is present in some of a person’s reproductive cells (eggs or sperm), but may be absent from most or all of their other body cells.

For example, a parent may have a pathogenic variant in a proportion of their sperm cells but have no symptoms themselves. If one of those sperm cells carries the variant and fertilises an egg, the child may inherit the variant in essentially all their cells.

This means that even when both parents have normal genetic test results from blood samples, there can occasionally be a risk of recurrence in another pregnancy because the genetic alteration may be present in their reproductive cells.

Gonadal mosaicism is particularly important in genetic counselling when:
– A family has more than one child affected by the same apparently de novo genetic condition.
– Both parents have tested negative for the child’s pathogenic variant in blood.
– A genetic condition is known to have a risk of parental germline mosaicism.
It is also possible for an individual to have both somatic and germline mosaicism, meaning the genetic change is present in some body cells and some reproductive cells.

Therefore, although most mosaicism arises spontaneously after conception, transmission to the next generation is possible when reproductive cells carry the genetic alteration.

[Author]

Posts