{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:46:36Z","timestamp":1787957196715,"version":"build-2784847793"},"reference-count":0,"publisher":"American Diabetes Association","issue":"2","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,2,1]]},"abstract":"<jats:p>Mutations of the insulin receptor gene are a cause of the type A syndrome of extreme insulin resistance. This study assessed the prevalence of such mutations in women with clinical features of the type A syndrome including ovarian hyperandrogenism, moderate-to-severe degrees of insulin resistance, and acanthosis nigricans. We studied 22 unrelated women with insulin resistance (fasting insulin &amp;gt;300 pM [50 \u03bcU\/ml] and\/or peak during an oral glucose tolerance test (OGTT) &amp;gt; 1,800 pM [300 \u03bcU\/ml]), acanthosis nigricans, and the polycystic ovary syndrome (hyperandrogenemia, oligoamenorrhea, and hirsutism). Two insulin-resistant probands with congenital generalized lipodystrophy and one male proband with severe insulin resistance also were included in the study. Southern blotting experiments were performed to exclude gross gene deletions, insertions, or rearrangements. Exons 2\u201322 of the insulin receptor gene were polymerase chain reaction (PCR) amplified from genomic DNA and screened for nucleotide variation using single-strand conformation polymorphism (SSCP). No nucleotide variation between study subjects was detected in exons 4\u20136, 10\u201312, 15, 16, 18, 19, or 21. Sequencing of amplified DNA revealed that SSCP variants in exons 2, 3, 8, 9, and 17 corresponded to known silent polymorphisms within the coding region. Variants in exons 2, 9, 13, and 14 were caused by novel silent polymorphisms; variants in exons 7 and 22 were caused by nucleotide substitutions in flanking introns. One proband was found to have a heterozygous point mutation in exon 20 (CGG\u2192CAG, Arg1174\u2192Gln) that involves the intracellular receptor \u03b2-subunit. Gin1174 is a novel mutant of the insulin receptor tyrosine kinase domain and is a likely cause of dominantly inherited insulin resistance. The mutation was present in an affected sister but was absent in the unaffected mother and 64 normal alleles. Two paternal aunts also are reportedly affected. The results of this study suggest that mutations at the insulin receptor locus are uncommon in insulin-resistant women with acanthosis nigricans and ovarian hyperandrogenism.<\/jats:p>","DOI":"10.2337\/diab.43.2.247","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:22:06Z","timestamp":1379611326000},"page":"247-255","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":55,"title":["Prevalence of Mutations in the Insulin Receptor Gene in Subjects With Features of the Type A Syndrome of Insulin Resistance"],"prefix":"10.2337","volume":"43","author":[{"given":"David E","family":"Moller","sequence":"first","affiliation":[{"name":"Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, the Department of Medicine at Beth Israel Hospital, and Harvard Medical School\u2008Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohad","family":"Cohen","sequence":"additional","affiliation":[{"name":"Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, the Department of Medicine at Beth Israel Hospital, and Harvard Medical School\u2008Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, the Department of Medicine at Beth Israel Hospital, and Harvard Medical School\u2008Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richardo","family":"Assiz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Biology, and Endocrinology, University of Alabama School of Medicine\u2008Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florin","family":"Grigorescu","sequence":"additional","affiliation":[{"name":"Biochimie Centre National de la Recherche Scientifique\u2014Institut National de la Sante et de la Recherche Medicate (CNRS-INSERM)\u2008Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Eberle","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, University of Tennessee Medical Center at Knoxville\u2008Knoxville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda A","family":"Morrow","sequence":"additional","affiliation":[{"name":"Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, the Department of Medicine at Beth Israel Hospital, and Harvard Medical School\u2008Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aorrow C","family":"Moses","sequence":"additional","affiliation":[{"name":"Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, the Department of Medicine at Beth Israel Hospital, and Harvard Medical School\u2008Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S","family":"Flier","sequence":"additional","affiliation":[{"name":"Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, the Department of Medicine at Beth Israel Hospital, and Harvard Medical School\u2008Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/43\/2\/247\/360727\/43-2-247.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/43\/2\/247\/360727\/43-2-247.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:25:16Z","timestamp":1667406316000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/43\/2\/247\/10417\/Prevalence-of-Mutations-in-the-Insulin-Receptor"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,2,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1994,2,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.43.2.247","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,2,1]]}}}