期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/ijms23105425
关键词
FMR1 gene; CGG repeat; mechanisms of instability; dynamic mutations; repeat expansion disorders; molecular medicine; neurological disease
资金
- PRIN [201789LFKB]
- MIUR-University Grant [D.1-2020]
A dynamic mutation in the FMR1 gene leads to Fragile X-related Disorders, primarily due to the expansion of an unstable CGG repeat sequence. Expansion events of the CGG sequence are more common than contractions, and the formation of abnormal secondary DNA structures may contribute to CGG expansion.
A dynamic mutation in exon 1 of the FMR1 gene causes Fragile X-related Disorders (FXDs), due to the expansion of an unstable CGG repeat sequence. Based on the CGG sequence size, two types of FMR1 alleles are possible: premutation (PM, with 56-200 CGGs) and full mutation (FM, with >200 triplets). Premutated females are at risk of transmitting a FM allele that, when methylated, epigenetically silences FMR1 and causes Fragile X syndrome (FXS), a very common form of inherited intellectual disability (ID). Expansions events of the CGG sequence are predominant over contractions and are responsible for meiotic and mitotic instability. The CGG repeat usually includes one or more AGG interspersed triplets that influence allele stability and the risk of transmitting FM to children through maternal meiosis. A unique mechanism responsible for repeat instability has not been identified, but several processes are under investigations using cellular and animal models. The formation of unusual secondary DNA structures at the expanded repeats are likely to occur and contribute to the CGG expansion. This review will focus on the current knowledge about CGG repeat instability addressing the CGG sequence expands.
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