FMR1 Iso-Seq: final files

<p>seng, E., Tang, H.-T., AlOlaby, R. R., Hickey, L. &amp; Tassone, F. Altered expression of the FMR1 splicing variants landscape in premutation carriers. <em>BBA - Gene Regulatory Mechanisms</em> <strong>1860,</strong> 1117&ndash;1126 (2017).</p> <p><em>FMR1</em> premutation carriers (55-200 CGG repeats) are at risk for developing Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), an adult onset neurodegenerative disorder. In addition, 20 % of female carriers will develop Fragile X-associated Primary Ovarian Insufficiency (FXPOI), in addition to a number of clinical problems affecting premutation carriers throughout their life span. Marked elevation in <em>FMR1</em> mRNA levels have been observed with premutation alleles resulting in RNA toxicity, the leading molecular mechanism proposed for the <em>FMR1</em> associated disorders observed in premutation carriers.</p> <p>The <em>FMR1</em> gene, undergoes alternative splicing and we have recently reported that the relative abundance of all <em>FMR1</em> mRNA isoforms is significantly increased in premutation carriers.</p> <p>In this study, we further investigated the transcriptional <em>FMR1</em> isoforms distribution pattern in different tissues and identified a total of 49 isoforms, some of which observed only in premutation carriers and which might play a role in the pathogenesis of FXTAS.</p> <p>Further, we investigated the distribution pattern and expression levels of the <em>FMR1</em> isoforms in asymptomatic premutation carriers and in those with FXTAS and found no significant difference between the two groups.</p> <p>Our findings suggest that the characterization of the expression levels of the different <em>FMR1</em> isoforms is fundamental for understanding the regulation of the <em>FMR1</em> gene as imbalance in their expression could lead to an altered functional diversity with neurotoxic consequences. Their characterization will also help to elucidating the mechanism(s) by which &ldquo;toxic gain of function&rdquo; of the <em>FMR1</em> mRNA may play a role in FXTAS and/or in the other <em>FMR1</em>-associated conditions.</p>