AI Article Synopsis
- - NF2-related schwannomatosis is a genetic condition that leads to the formation of multiple benign tumors, primarily schwannomas, due to inherited or new mutations in the NF2 gene.
- - The study highlights that over half of the new mutations in the NF2 gene (54%) occur at just six specific CpG sites, despite these sites making up less than 10% of all nonsense mutation positions.
- - Among these six CpG variants, one specific variant (c.586C>T; p.(Arg196Ter)) shows a significantly higher occurrence of new mutations compared to others, suggesting possible differences in how mutations arise during cellular reproduction.
Article Abstract
NF2-related schwannomatosis is an autosomal dominant tumour predisposition condition that causes multiple benign tumours of the nervous system, especially schwannomas. This results from germline pathogenic variants in the gene, which are most commonly de novo NF2 nonsense variants. Over half of these de novo variants occur at just six CpG dinucleotides. In this study, we show that the six CpG nonsense variants make up 54% (136/252) of de novo nonsense variants, despite constituting <10% of nonsense positions in the germline (total=62), and that this pattern is different from the gene, which is also known to have a high rate of mosaicism. In addition, the c.586C>T; p.(Arg196Ter) has a higher de novo heterozygote to mosaicism ratio than the five other CpG variants (73.1% vs 53.7%, p=0.03) and the neighbouring CpG variant ( c.592C>T; p.(Arg198Ter) 38.5%, p=0.02). This may be due to differences in rates of mutation at meiosis versus mitosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1136/jmg-2022-108960 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!