{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:30:03Z","timestamp":1788820203468,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations in the <jats:italic>GBA<\/jats:italic> gene that encodes the lysosomal enzyme acid \u03b2\u2010glucocerebrosidase cause Gaucher disease (GD), the most common lysosomal storage disorder. Most of the mutations are missense\/nonsense, however, a few splicing mutations within or close to conserved consensus donor or acceptor splice sites have also been described. The aim of the study was to identify the mutation(s) in a Cypriot patient with type I GD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The genomic DNA of the proband was screened for nine common mutations using Polymerase chain reaction\u2013restriction fragment length polymorphism (PCR\u2013RFLP) analysis. All exons and exon\u2010intron boundaries, and the 5\u2019UTR and 3\u2019UTR regions of the <jats:italic>GBA<\/jats:italic> gene, were investigated by Sanger sequencing. RNA analysis was performed using standard procedures, and the abnormal transcript was further cloned into pGEM\u2010T\u2010Easy plasmid vector and sequenced. The relevant intronic region was further sequenced by the Sanger method to identify the genetic variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel point mutation, g.12599C\u00a0&gt;\u00a0A (c.999\u00a0+\u00a0242C\u00a0&gt;\u00a0A), was detected deep in intron 7 of the <jats:italic>GBA<\/jats:italic> gene. This type of mutation has been previously described for other diseases but this is the first time, as far as we know, that it is described for GD. This mutation creates a new donor splice site leading to aberrant splicing and resulting in the insertion of the first 239nt of intron 7 as a pseudoexon in the mRNA, creating a premature stop codon.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study expands the mutation spectrum of GD and highlights the importance of RNA sequencing for the molecular diagnosis of patients bearing mutations in nonexonic regions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1090","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T17:44:15Z","timestamp":1579023855000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A novel mutation deep within intron 7 of the <i>GBA<\/i> gene causes Gaucher disease"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5918-9213","authenticated-orcid":false,"given":"Anna","family":"Malekkou","sequence":"first","affiliation":[{"name":"Department of Biochemical Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"},{"name":"Cyprus School of Molecular Medicine Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Sevastou","sequence":"additional","affiliation":[{"name":"Department of Biochemical Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavriella","family":"Mavrikiou","sequence":"additional","affiliation":[{"name":"Department of Biochemical Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Department of Biochemical Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"},{"name":"Cyprus School of Molecular Medicine Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lluisa","family":"Vilageliu","sequence":"additional","affiliation":[{"name":"Department of Genetics Faculty of Biology Universitat de Barcelona IBUB, CIBERER Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Moraitou","sequence":"additional","affiliation":[{"name":"Department of Enzymology and Cellular Function Institute of Child Health Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Michelakakis","sequence":"additional","affiliation":[{"name":"Department of Enzymology and Cellular Function Institute of Child Health Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrystalla","family":"Prokopiou","sequence":"additional","affiliation":[{"name":"Department of Haematology Limassol General Hospital Limassol Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5971-7637","authenticated-orcid":false,"given":"Anthi","family":"Drousiotou","sequence":"additional","affiliation":[{"name":"Department of Biochemical Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"},{"name":"Cyprus School of Molecular Medicine Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1100"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI105417"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770.2011.590172"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes7120133"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes9020073"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201787"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001315"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.20.7101"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.23.2679"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117084"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(89)90319-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00210743"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.564"},{"issue":"12","key":"e_1_2_9_15_1","first-page":"2675","article-title":"The missing puzzle piece: Splicing mutations","volume":"6","author":"Lewandowska M. 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