FRA2A Is a CGG Repeat Expansion Associated with Silencing of

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Some human genetic diseases are caused by dynamic mutations, or expansions of a short repeated sequence in the genome that can be unstably passed on from generation to generation. A subset of these dynamic mutations known as fragile sites can be seen as a break or gap on the chromosome when cells are cultured under specific conditions. To date eight folate-sensitive fragile sites (FSFS) have been characterized, and all are due to CGG-repeat expansions within the 5′ UTR or promoter region of the respective gene. When the repeat expands in size, it becomes hypermethylated and the adjacent gene or genes are transcriptionally silenced. For at least four of the eight known fragile sites this silencing of the associated gene(s) lead to intellectual disability syndromes such as fragile X. In this work we describe molecular characterization of an autosomal FSFS called FRA2A on chromosome 2. As the molecular cause of FRA2A, we identify an expansion of a CGG repeat which subsequently results in silencing of the neighbouring gene AFF3. This gene is one of the four autosomal paralogss of the AFF2/FMR2 gene which, when mutated, is the cause of the FRAXE syndrome. We find that FRA2A expression is associated with highly variable developmental anomalies in the three FRA2A families studied.

Vyšlo v časopise: FRA2A Is a CGG Repeat Expansion Associated with Silencing of. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004242
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004242

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