Mosaicism

A mosaic in the biological sense, also called a genetic mosaic or somatic mosaicism, refers to an individual whose cells have a different genetic makeup. Mosaics result from mutations in somatic cells after fertilization. Thus, they emerge from a homogeneous zygote (when cell populations are genetically different, they are called chimeras).

A genetic mosaic can affect all organs. If the skin is affected, such a mutation can lead to visible changes. A cutaneous mosaic is recognizable as a characteristic pattern (see Blaschko lines below) (Bae T et al. 2018).

Mosaics with chromosomal aberration are not uncommon in sex chromosomes as a result of loss of an X chromosome (e.g. Turner syndrome with karyotype 45,XO/46,XX).

As a result of X chromosome inactivation, females have a functional mosaic, with some of the maternal and some of the paternal X chromosome active in the cells. Many mosaic mutations are not detectable in the blood, but only in the affected tissue.

The detection of a postzygotic mosaic often means relief for parents of an affected child, as there is usually no increased risk of recurrence for further children. The child can only pass on the mutation to the next generation if its germ cells (egg or sperm cells) are also affected by the mosaic. In the case of inheritance, however, there is no mosaic but a continuous mutation in the offspring.

The severity and clinical symptoms of postzygotic mosaics depend on the time of the mutation event, the cell type in which the mutation occurs, the expansion of cells with mutation, the mutated gene and the mutation (Moog U et al. 2020). The later mosaics occur in embryonic development, the more limited the symptomatology. For example, certain hamartomas of the skin are due to local mosaics in skin cells (Happle R 2016).

The correct classification is important, because for some mosaic disorders, for example for "PIK3CA-related overgrowth spectrum" (PROS) with a PIK3CA inhibitor, molecular therapy approaches are already available.

1. Bae T et al. (2018) Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 359: 550-555

2. Lim YH et al (2017) Mosaicism in cutaneous disorders. Annu Rev Genet 51: 123-141
3. Moog U et al (2020) Diseases caused by genetic mosaicism. Dtsch Ärztebl Int 117: 119-125
4. Happle R (2016) The categories of cutaneous mosaicism: a proposed classification. Am J Med Genet A 170A: 452-459