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
Albright hereditary osteodystrophy is a rare syndrome, in which cutaneous and superficial soft tissue lesions traditionally include osteomas and calcifications. We report 4 patients from 2 families affected with Albright hereditary osteodystrophy and demonstrate that the spectrum of these cutaneous and soft tissue lesions is broader than is usually defined in the literature. In addition to osteomas in the dermis and subcutis, including so-called plaque-like osteoma, we identified the following lesions: calcifying aponeurotic fibroma-like lesion, calcinosis circumscripta-like lesion, and unusual nevi with osteoid and/or peculiar intranuclear pseudoinclusions. One osteoma and the calcifying aponeurotic fibroma-like lesion were analyzed by HUMARA and proved to be clonal. In a family, a novel mutation in the GNAS gene was also identified.
- MeSH
- dítě MeSH
- dospělí MeSH
- fibrom diagnóza genetika patologie MeSH
- fibrózní dysplazie polyostotická diagnóza genetika patologie MeSH
- kalcinóza diagnóza genetika patologie MeSH
- lidé MeSH
- mutace genetika MeSH
- nádory kostí diagnóza genetika patologie MeSH
- nádory kůže diagnóza genetika patologie MeSH
- névus diagnóza genetika patologie MeSH
- osteom diagnóza genetika patologie MeSH
- předškolní dítě MeSH
- proteiny vázající GTP - alfa-podjednotky Gs genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
