Blood expression profiles of fragile X premutation carriers identify genes involved in neurodegenerative and infertility phenotypes [FXTAS]

ABSTRACT: Fragile X premutation carriers (fXPC) of the CGG expansion in the 5M-bM-^@M-^Y-UTR of the fragile X mental retardation 1 (FMR1) gene are at high risk of Fragile X Tremor/Ataxia Syndrome (FXTAS), and females might undergo Premature Ovarian Failure (POF1). We have evaluated the peripheral blood gene expression profiles of fXPC and detected a strong deregulation of genes enriched in FXTAS-relevant biological pathways, including inflammation, and neuronal homeostasis and survival. More than 30% of differentially expressed correspond to long non-coding RNAs (lncRNAs). Several deregulated genes (CASP3, DFFA, APP, AKT1, COX6C, COX7B, SOD1, RNF10, HDAC5, ATXN7, ATXN3 and EAP1) were validated in brain samples of a mouse model of FXTAS and in neuronal cells expressing the expanded FMR1 5M-bM-^@M-^Y-UTR. One of the validated genes is the early at menopause 1 (EAP1) gene. We confirmed the EAP1 deregulation both in male and female fXPC. Down-regulation was stronger in female fXPC with POF1 compared with female fXPC without POF1. Increased levels of FMR1 mRNA were detected in all brain areas of the CGG-KI mouse model. EAP1 was significantly downregulated in the brainstem and cerebellum of the KI mouse, suggesting that EAP1 levels in certain brain areas could contribute to POF in this model. All together, these results suggest that gene expression profiling in blood of fXPC reflects changes in the brain transcriptome that may underlie neuropathological aspects in FXTAS and of POF. In the study presented here, we have 5 control samples plus one biological replicate and 9 patients with CGG expansions in the 5'UTR of the FMR1 gene (being premutation carriers)

ORGANISM(S): Homo sapiens

SUBMITTER: Elisabet Mateu Huertas 

PROVIDER: E-GEOD-48873 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress