{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:01:06Z","timestamp":1761102066163},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,8,21]],"date-time":"2013-08-21T00:00:00Z","timestamp":1377043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:p>Hereditary tyrosinemia type I (<jats:styled-content style=\"fixed-case\">HT1<\/jats:styled-content>) is a rare disease caused by a deficiency of fumarylacetoacetate hydrolase (<jats:italic><jats:styled-content style=\"fixed-case\">FAH<\/jats:styled-content><\/jats:italic>) in the tyrosine catabolic pathway, resulting mainly in hepatic alterations due to accumulation of the toxic metabolites fumarylacetoacetate, maleylacetoacetate and succinylacetone. We have characterized using minigenes four splicing mutations affecting exonic or intronic nucleotides of the <jats:italic><jats:styled-content style=\"fixed-case\">FAH<\/jats:styled-content><\/jats:italic> gene identified in two <jats:styled-content style=\"fixed-case\">HT1<\/jats:styled-content> patients. Two of the mutations are novel, c.82\u2010<jats:styled-content style=\"fixed-case\">1G<\/jats:styled-content>&gt;A and c.<jats:styled-content style=\"fixed-case\">913G<\/jats:styled-content>&gt;C and the other two have been previously associated with a splicing defect (c.<jats:styled-content style=\"fixed-case\">836A<\/jats:styled-content>&gt;G and c.1062+<jats:styled-content style=\"fixed-case\">5G<\/jats:styled-content>&gt;A). All mutations were confirmed to affect splicing in minigenes, resulting in exon skipping or activation of a cryptic splice site. We have analyzed the effect of different compounds known to modulate splicing (valproic acid, phenyl butyrate, <jats:styled-content style=\"fixed-case\">M344<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">EIPA<\/jats:styled-content>, and resveratrol) and the overexpression of splice factors of the <jats:styled-content style=\"fixed-case\">SR<\/jats:styled-content> protein family on the transcriptional profile of the mutant minigenes. For the c.<jats:styled-content style=\"fixed-case\">836A<\/jats:styled-content>&gt;G mutation, a partial recovery of the correctly spliced transcript was observed. These results confirm the relevance of performing functional studies for mutations potentially affecting the splicing process and open the possibility of supplementary therapeutic approaches to diseases caused by splicing defects.<\/jats:p>","DOI":"10.1111\/cge.12243","type":"journal-article","created":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T12:37:33Z","timestamp":1375101453000},"page":"167-171","source":"Crossref","is-referenced-by-count":13,"title":["Functional analysis and <i>in vitro<\/i> correction of splicing <i><scp>FAH<\/scp><\/i> mutations causing tyrosinemia type I"],"prefix":"10.1111","volume":"86","author":[{"given":"R.","family":"P\u00e9rez\u2010Carro","sequence":"first","affiliation":[{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares, Centro de Biolog\u00eda Molecular Severo Ochoa Universidad Aut\u00f3noma, CIBERER, IdiPaz Madrid 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