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FXS is caused by a trinucleotide repeat expansion in the 5\u2032 untranslated region of the\n                    <jats:italic>FMR1<\/jats:italic>\n                    gene, which leads to gene methylation, transcriptional silencing, and lack of expression of Fragile X Messenger Riboprotein (FMRP). Currently available FXS therapies are inefficient, and the disease severity is highly variable, making it difficult to predict disease trajectory and treatment response. We and others have recently shown that a subset of full-mutation, fully-methylated (FM\u2013FM) males with FXS express low amounts of FMRP which could contribute to phenotypic variability. To better understand the underlying mechanisms, we developed a sensitive qRT-PCR assay to detect\n                    <jats:italic>FMR1<\/jats:italic>\n                    mRNA in blood. This assay reproducibly detects trace amounts of\n                    <jats:italic>FMR1<\/jats:italic>\n                    mRNA in a subset of FM\u2013FM males, suggesting that current Southern Blot and PCR determination of FM\u2013FM status is not always associated with complete transcriptional silencing. The functional relevance of trace-level\n                    <jats:italic>FMR1<\/jats:italic>\n                    mRNA is confirmed by showing a positive correlation with cognitive function; however, phenotypic variability is not fully explained by\n                    <jats:italic>FMR1<\/jats:italic>\n                    expression. These results corroborate the need for better molecular assays for FXS diagnosis and encourage studies to elucidate the factors contributing to the phenotypic variability of FXS.\n                  <\/jats:p>","DOI":"10.1038\/s41598-023-29786-4","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T07:06:35Z","timestamp":1678172795000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A sensitive and reproducible qRT-PCR assay detects physiological relevant trace levels of FMR1 mRNA in individuals with Fragile X syndrome"],"prefix":"10.1038","volume":"13","author":[{"given":"Devan","family":"Straub","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E.","family":"Boggs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli C.","family":"Dominick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Erickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"29786_CR1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1146\/annurev.genom.8.080706.092249","volume":"8","author":"O Penagarikano","year":"2007","unstructured":"Penagarikano, O., Mulle, J. 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