Genomic Mosaicism in Human Development and Diseases
A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".
Deadline for manuscript submissions: 15 June 2024 | Viewed by 2735
Special Issue Editor
Special Issue Information
Dear Colleagues,
Genomic mosaicism defines the phenomenon that different tissues and organs from the same individual present different genomic sequences. Mosaicism is a result of postzygotic mutations occurring during embryonic development, tissue self-renewal, environmental toxicity, aging, and disease. The failure to repair these mutations will leave them in the genome throughout one’s lifespan, and the mutations will be inherited by all the carrier’s daughter cells.
On the one hand, neutral or near-neutral genomic mosaic mutations can serve as recorders of human embryonic development. They are naturally barcoding the developmental cell clones, helping researchers to reconstruct lineage distribution patterns of early embryonic development.
On the other hand, emerging evidence has demonstrated that mosaic mutations are important genetic origins of disease. Cancer driver mutations have already shown to be detectable on adjacent tissues that are apparently normal. Apart from skin and skeletal disorders where mosaic mutations are already a known cause, developmental disorders and autoimmune disorders have also been demonstrated to be caused by mosaic mutations.
In this Special Issue, submissions on the following, but not limited to, topics are welcome:
● Mosaicism in human development;
● Somatic mosaicism that directly causes human disorders;
● Pre-disease mosaic mutation burdens for different disorders;
● Methodologies for mosaic studies.
Dr. Xiaoxu Yang
Guest Editor
Manuscript Submission Information
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Keywords
- mosaicism
- mutations
- development
- disorder
- cancer
Planned Papers
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: Preimplantation Genetic Testing Identifies Patient with Mosaic Li Fraumeni Syndrome That Eludes Germinal Tissues.
Abstract:
Li Fraumeni syndrome (LFS) is a hereditary multi-cancer syndrome caused by alterations of the TP53 gene. Next generation sequencing (NGS) allows for the detection of TP53 variants at lower variant allele frequencies (VAFs). A low VAF TP53 variant may represent mosaic LFS or aberrant clonal expansion (ACE). Differentiation between these two conditions is important to provide optimal patient care. Here, we describe a female patient with a history of adrenocortical neoplasm and osteosarcoma, diagnosed at 2 and 16 years of age, respectively. Testing on peripheral blood identified a pathogenic variant, TP53 c.733G>A (p.G245S). Subsequent in vitro fertilization with preimplantation genetic testing for monogenic disorders (PGT-M) did not identify this TP53 variant in any of ten embryos tested. Ancillary testing for possible mosaicism in the proband was performed on four different specimens, revealing variable allele frequencies of the TP53 variant (saliva: 44%; blood: 31%; skin fibroblasts: 18%; and colon tissue: 9%). These results suggest a post-zygotic event, consistent with mosaic LFS rather than ACE. This case highlights the complexity of interpreting mosaic variants in the TP53 gene, and the difficulty in relaying cancer and reproductive risk information in the context of mosaicism.