PMC8165229_01
PMC8165229_02
PMC8165229_03
PMC8165229_04
Embryonic de novo mutations can result in highly variable phenotypes due to mosaicism. Individuals who acquire a mutation at the 4-cell stage, represented by the yellow star, may experience symptoms in all cell types (given that the variant in question has equal ability to affect all cell types). A variant acquired at the gastrula stage, represented by the black star, may only affect one germ layer and therefore a more restricted subset of cell types. In this example, the black mutation may only affect heart, muscle, kidney, skin, and bones, but not neuronal tissue. In the case of TS, this is a possible mechanism for cases that have symptoms restricted to LTQ and syndactyly. A variant that arises after germ cells have been set aside, represented by the red star, may only affect germ cells, and therefore may not cause phenotypes in the individual, but may affect the individual's children. Adapted from "Human Embryonic Stem Cell Differentiation," by BioRender.com (2020). Retrieved from: https://app.Biorender.com/biorender-templates.
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Additionally, depending on the timing and location of an embryonic de novo variant, certain germ layers or cell lineages could be differentially affected (Figure 3).