{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:32:29Z","timestamp":1745469149760,"version":"3.40.4"},"reference-count":25,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2015]]},"abstract":"<b><i>Background\/Aims:<\/i><\/b> Donohue syndrome is an extremely rare autosomal recessive disorder caused by mutations in <i>INSR<\/i>. This study describes the clinical course of a patient with Donohue syndrome, and we also evaluated the molecular and functional characteristics of 2 novel <i>INSR<\/i> mutations. <b><i>Methods:<\/i><\/b> Our patient was a male newborn with acanthosis nigricans, lack of subcutaneous fat, hirsutism, thick lips, and high serum insulin levels, all of which are characteristic of Donohue syndrome. <i>INSR<\/i> mutation analysis was performed, and Western blot analysis was used to verify the effects of the novel mutations on INSR protein expression. <b><i>Results:<\/i><\/b> Direct <i>INSR<\/i> sequencing identified the following 2 novel compound heterozygous mutations in the \u03b2-subunit of <i>INSR<\/i>: p.Arg1066* and p.Gln1232*. Western blot analysis of skin fibroblasts revealed a comparable expression of the \u03b1-subunit of INSR in mutant and control samples, but reduced levels of mature INSR \u03b2-subunit protein were found in mutant INSR-expressing cells in comparison to the controls. <b><i>Conclusions:<\/i><\/b> This study describes the clinical course of a male patient with Donohue syndrome and the molecular characteristics of 2 novel compound heterozygous mutations in <i>INSR<\/i>. These novel nonsense mutations are associated with reduced expression of the mature INSR \u03b2-subunit, which was most likely due to impaired proreceptor processing.<\/jats:p>","DOI":"10.1159\/000381624","type":"journal-article","created":{"date-parts":[[2015,7,7]],"date-time":"2015-07-07T21:01:33Z","timestamp":1436302893000},"page":"73-78","source":"Crossref","is-referenced-by-count":3,"title":["Identification and Functional Characterization of Two Novel Nonsense Mutations in the \u03b2-Subunit of <b><i>INSR<\/i><\/b> That Cause Severe Insulin Resistance Syndrome"],"prefix":"10.1159","volume":"84","author":[{"given":"Jin-Ho","family":"Choi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minji","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja Hye","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jahyang","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gu-Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Wook","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2015,7,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/313756a0"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.47.8.1362"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(03)00142-5"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1007\/s004310050594"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3215"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0020"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1159\/000366225"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-012-1901-7"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.79.3.8077364"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.8.5902"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/0898-6568(92)90030-C"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ12-0289"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2012.27.5.565"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1210\/er.13.3.566"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.12.1465"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000133625.73570.54"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030034"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.02.013"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1992.tb00945.x"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199109263251307"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050695"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2006.02678.x"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.2.542"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-07-0271"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2088"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/381624","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/381624","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:56:00Z","timestamp":1745430960000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000381624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,9,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000381624","archive":["Portico"],"relation":{},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"type":"print","value":"1663-2818"},{"type":"electronic","value":"1663-2826"}],"subject":[],"published":{"date-parts":[[2015]]}}}