{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:42:48Z","timestamp":1789425768411,"version":"build-2803163510"},"reference-count":31,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ophthalmic Res"],"published-print":{"date-parts":[[2005]]},"abstract":"<jats:p>Dominant optic atrophy (DOA) is the most common form of inherited primary optic neuropathy. The purpose of the current study was to report a novel &lt;i&gt;OPA1&lt;\/i&gt; splice site mutation and investigate the impact of the mutation on pre-mRNA splicing in a female proband and her father diagnosed with DOA. We evaluated visual acuity, retinal fundi and kinetic visual fields. Color vision phenotypes were determined using the Farnsworth Panel D-15 and the Farnsworth-Munsell 100-hue tests. All 28 coding exons of the &lt;i&gt;OPA1&lt;\/i&gt; gene were analyzed with polymerase chain reaction (PCR) amplification and direct sequencing. Total RNA extraction from white blood cells followed by reverse transcription-PCR (RT-PCR) was performed. We identified a novel heterozygous G to A mutation at position +1 of intron 20 (g.IVS20+1G\u2192A) in both patients. RT-PCR analysis revealed that the first 25 bp from intron 20 plus exon 20 were spliced onto exon 21. No difference in expression of mutant and wild-type transcripts was found within the linear range of amplification. Clinically, both patients exhibited reduced visual acuities, pallor of optic discs, decreased sensitivities of central visual fields and blue-yellow color vision defects. Previously, only one mechanism (skipping of exon) of pre-mRNA splicing defects has been reported among &lt;i&gt;OPA1&lt;\/i&gt; splice site mutations. Our study demonstrates that the mechanism of intron retention is a novel type of pre-mRNA splicing defects. The mutant transcript with a premature termination codon is likely to encode a truncated protein, due to a translational frameshift (V672fsX675), that lacks 289 amino acids of the C-terminal end. Therefore, it is suggested that haploinsufficiency underlies DOA in the patients. However, we could not exclude the possibility that the truncated protein has a dominant negative activity because the mutant transcript is insusceptible to nonsense-mediated mRNA decay.<\/jats:p>","DOI":"10.1159\/000086862","type":"journal-article","created":{"date-parts":[[2005,7,8]],"date-time":"2005-07-08T14:15:41Z","timestamp":1120832141000},"page":"214-224","source":"Crossref","is-referenced-by-count":11,"title":["Dominant Optic Atrophy Caused by a Novel &lt;i&gt;OPA1&lt;\/i&gt; Splice Site Mutation (IVS20+1G\u2192A) Associated with Intron Retention"],"prefix":"10.1159","volume":"37","author":[{"given":"Takaaki","family":"Hayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamaki","family":"Gekka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Omoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokazu","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kitahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2005,7,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3109%2F13816818809031474"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1136%2Fjmg.35.10.793"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1755-3768.1983.tb01424.x"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1136%2Fbjo.75.1.49"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1023%2FA%3A1001844021014"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1093%2Fhmg%2F3.6.977"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038%2F79944"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038%2F79936"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016%2FS0021-5155%2802%2900484-7"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016%2FS0002-9394%2802%2901929-3"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016%2FS0021-5155%2803%2900056-X"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1101%2Fgad.6.3.380"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1006%2Fbbrc.1998.9539"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1083%2Fjcb.143.2.351"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1093%2Fhmg%2F10.13.1359"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00439-001-0633-y"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1002%2Fhumu.9152"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016%2F0378-1119%2894%2990567-3"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1093%2Fhmg%2F10.13.1369"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002%2F%28SICI%291098-1004%28200001%2915%3A1%3C7%3A%3AAID-HUMU4%3E3.0.CO%3B2-N"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1080%2F02713689808951221"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1023%2FA%3A1017553532092"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1007%2FBF00210743"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2801%2900202-1"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016%2FS0968-0004%2898%2901208-0"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1038%2Fnrm1310"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1006%2Fmgme.2001.3278"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1167%2Fiovs.02-0333"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.C200677200"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1091%2Fmbc.E04-04-0294"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M400920200"}],"container-title":["Ophthalmic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/86862","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/86862","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:16:32Z","timestamp":1745464592000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000086862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2005,8,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000086862","archive":["Portico"],"relation":{},"ISSN":["0030-3747","1423-0259"],"issn-type":[{"value":"0030-3747","type":"print"},{"value":"1423-0259","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005]]}}}