{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:31:15Z","timestamp":1790605875453,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,2,3]],"date-time":"2016-02-03T00:00:00Z","timestamp":1454457600000},"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":[[2016,10]]},"abstract":"Danon disease (DD<\/jats:styled-content>) is a rare X\u2010linked multisystem disorder caused by mutations of the LAMP2<\/jats:italic><\/jats:styled-content> gene and characterized by intellectual disability, skeletal myopathy and cardiomyopathy. The survival time is severely reduced. Contrasting with the usual disease course, we report on a family with an exceptionally mild phenotype of DD<\/jats:styled-content> despite having two potentially damaging LAMP2<\/jats:italic><\/jats:styled-content> mutations. Using RNA<\/jats:styled-content>\u2010Seq analysis, we showed that a c.65\u20102A<\/jats:styled-content>>G splice site mutation results in the tissue\u2010specific production of four different transcripts including the full\u2010length mRNA<\/jats:styled-content> in muscle tissue but not in leukocytes. We confirmed our results by immunohistochemistry and immunoblotting, showing the detection of LAMP2<\/jats:styled-content> protein only in muscle. The second mutation (c.586A<\/jats:styled-content>>T, p.T196S<\/jats:styled-content>) has been reported before to have an uncertain clinical significance. In our patients, however, neither of the two mutations seem to have a high enough functional impact to cause a severe phenotype. Overall, our study reveals that alternative splicing is a potential mechanism in DD<\/jats:styled-content> with underlying splice site mutations of the LAMP2<\/jats:italic><\/jats:styled-content> gene in order to rescue the full\u2010length mRNA<\/jats:styled-content>. Moreover, our report of a mild phenotype complements the DD<\/jats:styled-content> spectrum, which is of great importance for a rare disease suspected to be underdiagnosed.<\/jats:p>","DOI":"10.1111\/cge.12724","type":"journal-article","created":{"date-parts":[[2016,1,10]],"date-time":"2016-01-10T09:40:13Z","timestamp":1452418813000},"page":"366-371","source":"Crossref","is-referenced-by-count":14,"title":["The c.65\u20102A>G splice site mutation is associated with a mild phenotype in Danon disease due to the transcription of normal LAMP2 mRNA"],"prefix":"10.1111","volume":"90","author":[{"given":"H.","family":"Cetin","sequence":"first","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"W\u00f6hrer","sequence":"additional","affiliation":[{"name":"Institute of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Rittelmeyer","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Gencik","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Zulehner","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Zimprich","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Str\u00f6bel","sequence":"additional","affiliation":[{"name":"Institute of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Zimprich","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31820ad795"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5724"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2745"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001105"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033349"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9251-y"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.5414\/NP300465"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.12.5463"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199410133311503"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2007.12.005"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000309219.61785.b3"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.546481"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12724","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12724","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T21:32:43Z","timestamp":1696368763000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,3]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1111\/cge.12724"],"URL":"https:\/\/doi.org\/10.1111\/cge.12724","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,3]]}}}