Mutations occurring during embryonic development affect only a subset of cells resulting in two or more distinct cell populations that are present at different levels, also known as postzygotic mosaicism (PZM). Although PZM is a common biological phenomenon, it is often overlooked as a source of disease due to the challenges associated with its detection and characterization, especially for very low-frequency variants. Moreover, PZM can cause a different phenotype compared to constitutional mutations. Especially, lethal mutations in receptor tyrosine kinase (RTK) pathway genes, which exist only in a mosaic state, can have completely new clinical manifestations and can look very different from the associated monogenic disorder. However, some key questions are still not addressed, such as the level of mosaicism resulting in a pathogenic phenotype and how the clinical outcome changes with the development and age. Addressing these questions is not trivial as we require methods with the sensitivity to capture some of these variants hidden away in very few cells. Recent ultra-accurate deep-sequencing approaches can now identify these low-level mosaics and will be central to understand systemic and local effects of mosaicism in the RTK pathway. The main focus of this review is to highlight the importance of low-level mosaics and the need to include their detection in studies of genomic variation associated with disease.
- MeSH
- dítě MeSH
- embryo savčí MeSH
- exprese genu MeSH
- fenotyp MeSH
- fibrózní dysplazie polyostotická enzymologie genetika patologie MeSH
- fosfatidylinositol-3-kinasy třídy I genetika metabolismus MeSH
- kojenec MeSH
- letální geny MeSH
- lidé MeSH
- mozaicismus * MeSH
- novorozenec MeSH
- Proteův syndrom enzymologie genetika patologie MeSH
- signální transdukce MeSH
- Sturgeův-Weberův syndrom enzymologie genetika patologie MeSH
- tyrosinkinasové receptory nedostatek genetika MeSH
- zárodečné mutace * MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
