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<title>
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Entry
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- #610549 - DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
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- OMIM
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS) OR (INSR)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=1251&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/8675" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/type-a-insulin-resistance-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=610549[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2297" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 237606005<br />
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<strong>ORPHA:</strong> 2297<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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610549
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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INSULIN RECEPTOR, DEFECT IN, WITH INSULIN-RESISTANT DIABETES MELLITUS AND ACANTHOSIS NIGRICANS<br />
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DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS, TYPE A<br />
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IRAN, TYPE A
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</span>
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</h4>
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</div>
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<div>
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<br />
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</div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/19/202?start=-3&limit=10&highlight=202">
|
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19p13.2
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Diabetes mellitus, insulin-resistant, with acanthosis nigricans
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/610549"> 610549 </a>
|
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</span>
|
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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INSR
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/147670"> 147670 </a>
|
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<p>A number sign (#) is used with this entry because insulin-resistant diabetes mellitus with acanthosis nigricans can be caused by heterozygous, homozygous, or compound heterozygous mutation in the INSR gene (<a href="/entry/147670">147670</a>) on chromosome 19p13.</p>
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<p><a href="#6" class="mim-tip-reference" title="Kahn, C. R., Flier, J. S., Bar, R. S., Archer, J. A., Gorden, P., Martin, M. M., Roth, J. <strong>The syndromes of insulin resistance and acanthosis nigricans: insulin receptor disorders in man.</strong> New Eng. J. Med. 294: 739-745, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/176581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">176581</a>] [<a href="https://doi.org/10.1056/NEJM197604012941401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="176581">Kahn et al. (1976)</a> divided the syndrome of insulin resistance and acanthosis nigricans into two: type A, a syndrome of younger females with signs of virilization and accelerated growth in whom a defect in cell receptors for insulin may be primary; and type B, a syndrome in older females with signs of an immunologic disease in whom circulating antibodies to the insulin receptor are found. Although no familial cases were found, they commented that all their patients and those in the literature were female; most were black, although the syndrome has been observed in persons of American Indian, Italian, Venezuelan, and Japanese origin. Despite insulin resistance, ketoacidosis was rare. Females with the type A syndrome have polycystic ovaries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=176581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Rudiger, H. W., Dreyer, M., Kuhnau, J., Bartelheimer, H. <strong>Familial insulin-resistant diabetes secondary to an affinity defect of the insulin receptor.</strong> Hum. Genet. 64: 407-411, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6352462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6352462</a>] [<a href="https://doi.org/10.1007/BF00292378" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6352462">Rudiger et al. (1983)</a> described 3 sibs with mild diabetes in combination with acanthosis nigricans and minor physical abnormalities: bitemporal narrowing of the skull, paucity of body fat, acral hypertrophy (enlarged ears, nose, chin, and finger tips), brachydactyly, protrusion of the eye globes, and dental anomalies (supernumerary teeth, severe and premature caries, abnormally prominent lower canines and upper incisors). Fasting plasma insulin was 100 times normal. Insulin-binding was defective. Scatchard analysis showed a normal number of insulin-binding sites per cell but a complete lack of insulin binding to the high-affinity receptor component. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6352462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In patients with an inherited affinity defect of the insulin receptor, <a href="#14" class="mim-tip-reference" title="Rudiger, H. W., Ahrens, P., Dreyer, M., Frorath, B., Loffel, C., Schmidt-Preuss, U. <strong>Impaired insulin-induced RNA synthesis secondary to a genetically defective insulin receptor.</strong> Hum. Genet. 69: 76-78, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2578425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2578425</a>] [<a href="https://doi.org/10.1007/BF00295533" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2578425">Rudiger et al. (1985)</a> found that stimulation of glucose uptake, an early effect of insulin, was normal, but insulin-mediated stimulation of RNA synthesis, a late effect, was defective. Both the affinity defect and the deficient stimulation of RNA synthesis were apparent at low concentrations of insulin only and disappeared at very high concentrations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2578425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Mariani, S., Pedone, A., Meschi, F., Di Natale, B., Caputo, R., Broggi, U., Chiumello, G. <strong>Insulin resistance in a child with acanthosis nigricans type A.</strong> Acta Paediat. Scand. 71: 667-670, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7136687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7136687</a>] [<a href="https://doi.org/10.1111/j.1651-2227.1982.tb09496.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7136687">Mariani et al. (1982)</a> described a 6.3-year-old girl with acanthosis nigricans, insulin-resistant diabetes mellitus, hypertelorism, prognathism, macroglossia, and large ears. Generalized hypertrichosis and hypertrophy of the clitoris were present. A decrease in the number of insulin receptors was demonstrated. In the patient reported by <a href="#8" class="mim-tip-reference" title="Leme, C. E., Wajchenberg, B. L., Lerario, A. C., Goldman, J., Borges, J. L. C. <strong>Acanthosis nigricans, hirsutism, insulin resistance and insulin receptor defect.</strong> Clin. Endocr. 17: 43-49, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6749340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6749340</a>] [<a href="https://doi.org/10.1111/j.1365-2265.1982.tb02632.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6749340">Leme et al. (1982)</a>, polycystic ovaries were also present. Insulin resistance with acanthosis nigricans but with normal receptors may have a postreceptor defect (<a href="#1" class="mim-tip-reference" title="Bar, R. S., Muggeo, M., Roth, J., Kahn, C. R., Havrankova, J., Imperato-McGinley, J. <strong>Insulin resistance, acanthosis nigricans, and normal insulin receptors in a young woman: evidence for a postreceptor defect.</strong> J. Clin. Endocr. Metab. 47: 620-625, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/400728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">400728</a>] [<a href="https://doi.org/10.1210/jcem-47-3-620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="400728">Bar et al., 1978</a>). <a href="#13" class="mim-tip-reference" title="Prince, M. J., Smith, F. E., Peters, E. J., Stuart, C. A. <strong>Functional characteristics of decreased insulin receptors on fibroblasts obtained from a subject with severe insulin resistance and acanthosis nigricans.</strong> Diabetes 35: 148-154, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3510921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3510921</a>] [<a href="https://doi.org/10.2337/diab.35.2.148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3510921">Prince et al. (1986)</a> studied a 15-year-old black female with menstrual irregularity, mild hirsutism, and marked acanthosis nigricans that was first noted at age 4 years. Insulin receptors on cultured fibroblasts were decreased and the remaining receptors showed a functional impairment. Perhaps one should speak of types A1 and A2 of insulin-resistance and acanthosis nigricans (IRAN), type A2 being a form with a postbinding defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3510921+400728+7136687+6749340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Grigorescu, F., Flier, J. S., Kahn, C. R. <strong>Defect in insulin receptor phosphorylation in erythrocytes and fibroblasts associated with severe insulin resistance.</strong> J. Biol. Chem. 259: 15003-15006, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6392291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6392291</a>]" pmid="6392291">Grigorescu et al. (1984)</a> and <a href="#5" class="mim-tip-reference" title="Grunberger, G., Zick, Y., Gordon, G. <strong>Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding.</strong> Science 223: 932-934, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6141638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6141638</a>] [<a href="https://doi.org/10.1126/science.6141638" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6141638">Grunberger et al. (1984)</a> described patients with type A insulin resistance and decreased insulin receptor kinase activity. In 2 patients with type A extreme insulin resistance, sisters who were the products of a consanguineous marriage, <a href="#12" class="mim-tip-reference" title="Ojamaa, K., Hedo, J. A., Roberts, C. T., Jr., Moncada, V. Y., Gorden, P., Ullrich, A., Taylor, S. I. <strong>Defects in human insulin receptor gene expression.</strong> Molec. Endocr. 2: 242-247, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2840573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2840573</a>] [<a href="https://doi.org/10.1210/mend-2-3-242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2840573">Ojamaa et al. (1988)</a> found normal levels of insulin receptor mRNA. They had previously shown that the insulin receptor precursor is synthesized at a normal rate in these patients, thus suggesting a defect in the posttranslational processing of the receptor or in its translocation to the plasma membrane. See review by <a href="#7" class="mim-tip-reference" title="Kahn, C. R., White, M. F. <strong>The insulin receptor and the molecular mechanism of insulin action.</strong> J. Clin. Invest. 82: 1151-1156, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3049671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3049671</a>] [<a href="https://doi.org/10.1172/JCI113711" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3049671">Kahn and White (1988)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2840573+3049671+6392291+6141638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Schwenk, W. F., Rizza, R. A., Mandarino, L. J., Gerich, J. E., Hayles, A. B., Haymond, M. W. <strong>Familial insulin resistance and acanthosis nigricans: presence of a postbinding defect.</strong> Diabetes 35: 33-37, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3510137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3510137</a>] [<a href="https://doi.org/10.2337/diab.35.1.33" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3510137">Schwenk et al. (1986)</a> observed acanthosis nigricans in a white family; the mother and 3 daughters (including a set of identical twins) had acanthosis nigricans. Three sons were normal. Two of the 4 affected females had no apparent ovarian dysfunction, whereas 2 had hyperprolactinemia without other findings of polycystic ovary disease (<a href="/entry/184700">184700</a>). The twins had muscle cramps (see <a href="/entry/200170">200170</a>). All had normal red cell and monocyte binding of insulin. Insulin responsiveness, on the other hand, was reduced, suggesting a postbinding defect. They raised the question of autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3510137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Seemanova, E., Rudiger, H. W., Dreyer, M. <strong>Autosomal dominant insulin resistance syndrome due to a postbinding defect.</strong> Am. J. Med. Genet. 44: 705-712, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1282780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1282780</a>] [<a href="https://doi.org/10.1002/ajmg.1320440602" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1282780">Seemanova et al. (1992)</a> investigated a family in which at least 4 men in 3 generations had a syndrome of obesity, mild mental retardation, delayed puberty, macroorchidism, acanthosis nigricans, hyperinsulinemia, and, later, overt insulin-resistant diabetes mellitus (noninsulin-dependent diabetes mellitus, or type II diabetes). The patients had markedly curly scalp hair and deficient hair of the face and body. Teeth were normal. There was normal insulin binding to fibroblasts; however, insulin-stimulated RNA synthesis was decreased as compared to that of normal control individuals, suggesting a postbinding defect in insulin action. The pedigree showed an autosomal dominant pattern of inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1282780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a young Japanese male with insulin-resistant diabetes mellitus and acanthosis nigricans, <a href="#11" class="mim-tip-reference" title="Odawara, M., Kadowaki, T., Yamamoto, R., Shibasaki, Y., Tobe, K., Accili, D., Bevins, C., Mikami, Y., Matsuura, N., Akanuma, Y., Takaku, F., Taylor, S. I., Kasuga, M. <strong>Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor.</strong> Science 245: 66-68, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2544998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2544998</a>] [<a href="https://doi.org/10.1126/science.2544998" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2544998">Odawara et al. (1989)</a> identified a mutation in the INSR gene (<a href="/entry/147670#0001">147670.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2544998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 22 unrelated women with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (hyperandrogenemia, oligoamenorrhea, and hirsutism), <a href="#10" class="mim-tip-reference" title="Moller, D. E., Cohen, O., Yamaguchi, Y., Assiz, R., Grigorescu, F., Eberle, A., Morrow, L. A., Moses, A. C., Flier, J. S. <strong>Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance.</strong> Diabetes 43: 247-255, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8288049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8288049</a>] [<a href="https://doi.org/10.2337/diab.43.2.247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8288049">Moller et al. (1994)</a> identified only 1 mutation in the INSR gene: arg1174 to gln (<a href="/entry/147670#0030">147670.0030</a>). <a href="#10" class="mim-tip-reference" title="Moller, D. E., Cohen, O., Yamaguchi, Y., Assiz, R., Grigorescu, F., Eberle, A., Morrow, L. A., Moses, A. C., Flier, J. S. <strong>Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance.</strong> Diabetes 43: 247-255, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8288049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8288049</a>] [<a href="https://doi.org/10.2337/diab.43.2.247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8288049">Moller et al. (1994)</a> concluded that mutation in the INSR gene is a rare cause of the type A syndrome of extreme insulin resistance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8288049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Acanthosis nigricans in association with insulin resistance behaves as either a dominant (e.g., <a href="/entry/147670#0001">147670.0001</a>) or a recessive (e.g., <a href="/entry/147670#0004">147670.0004</a>). The polycystic ovary syndrome is sometimes associated. The autosomal dominant mutations in the insulin receptor gene are 'dominant negatives;' the mutant receptor protein interferes with the function of the normal receptor.</p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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<a href="#2" class="mim-tip-reference" title="Dash, S., Sano, H., Rochford, J. J., Semple, R. K., Yeo, G., Hyden, C. S. S., Soos, M. A., Clark, J., Rodin, A., Langenberg, C., Druet, C., Fawcett, K. A., Tung, Y. C. L., Wareham, N. J., Barroso, I., Lienhard, G. E., O'Rahilly, S., Savage, D. B. <strong>A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia.</strong> Proc. Nat. Acad. Sci. 106: 9350-9355, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19470471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19470471</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19470471[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0900909106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19470471">Dash et al. (2009)</a> screened 156 severely insulin-resistant patients with acanthosis nigricans for mutations in the candidate gene TBC1D4 (<a href="/entry/612465">612465</a>) and identified a 23-year-old woman who was heterozygous for a nonsense mutation (R363X; <a href="/entry/612465#0001">612465.0001</a>). The mutation was present in her affected half sister, as well as in their mother and a maternal aunt, neither of whom exhibited acanthosis nigricans but who did have a disproportionate rise in insulin following oral glucose load. Their maternal grandmother, who also carried the mutation, showed a normal peak-to-fasting insulin ratio but had an elevated fasting glucose and impaired glucose tolerance, indicative of significant beta-cell dysfunction. The mutation was not found in an unaffected aunt who was obese but had normal glucose tolerance and a normal peak-to-fasting insulin ratio, or in 200 ethnically matched alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19470471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Grigorescu1986" class="mim-tip-reference" title="Grigorescu, F., Flier, J. S., Kahn, C. R. <strong>Characterization of binding and phosphorylation defects of erythrocyte insulin receptors in the type A syndrome of insulin resistance.</strong> Diabetes 35: 127-138, 1986.">Grigorescu et al. (1986)</a>
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<li>
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<a id="1" class="mim-anchor"></a>
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<a id="Bar1978" class="mim-anchor"></a>
|
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|
|
<p class="mim-text-font">
|
|
Bar, R. S., Muggeo, M., Roth, J., Kahn, C. R., Havrankova, J., Imperato-McGinley, J.
|
|
<strong>Insulin resistance, acanthosis nigricans, and normal insulin receptors in a young woman: evidence for a postreceptor defect.</strong>
|
|
J. Clin. Endocr. Metab. 47: 620-625, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/400728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">400728</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=400728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1210/jcem-47-3-620" target="_blank">Full Text</a>]
|
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|
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<a id="Dash2009" class="mim-anchor"></a>
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Dash, S., Sano, H., Rochford, J. J., Semple, R. K., Yeo, G., Hyden, C. S. S., Soos, M. A., Clark, J., Rodin, A., Langenberg, C., Druet, C., Fawcett, K. A., Tung, Y. C. L., Wareham, N. J., Barroso, I., Lienhard, G. E., O'Rahilly, S., Savage, D. B.
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<strong>A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia.</strong>
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Proc. Nat. Acad. Sci. 106: 9350-9355, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19470471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19470471</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19470471[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19470471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0900909106" target="_blank">Full Text</a>]
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<a id="Grigorescu1984" class="mim-anchor"></a>
|
|
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|
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Grigorescu, F., Flier, J. S., Kahn, C. R.
|
|
<strong>Defect in insulin receptor phosphorylation in erythrocytes and fibroblasts associated with severe insulin resistance.</strong>
|
|
J. Biol. Chem. 259: 15003-15006, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6392291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6392291</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6392291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Grigorescu1986" class="mim-anchor"></a>
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<p class="mim-text-font">
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Grigorescu, F., Flier, J. S., Kahn, C. R.
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<strong>Characterization of binding and phosphorylation defects of erythrocyte insulin receptors in the type A syndrome of insulin resistance.</strong>
|
|
Diabetes 35: 127-138, 1986.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3510919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3510919</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3510919" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.2337/diab.35.2.127" target="_blank">Full Text</a>]
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<a id="Grunberger1984" class="mim-anchor"></a>
|
|
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|
|
Grunberger, G., Zick, Y., Gordon, G.
|
|
<strong>Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding.</strong>
|
|
Science 223: 932-934, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6141638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6141638</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6141638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.6141638" target="_blank">Full Text</a>]
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|
|
Kahn, C. R., Flier, J. S., Bar, R. S., Archer, J. A., Gorden, P., Martin, M. M., Roth, J.
|
|
<strong>The syndromes of insulin resistance and acanthosis nigricans: insulin receptor disorders in man.</strong>
|
|
New Eng. J. Med. 294: 739-745, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/176581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">176581</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=176581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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|
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[<a href="https://doi.org/10.1056/NEJM197604012941401" target="_blank">Full Text</a>]
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|
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|
|
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|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kahn, C. R., White, M. F.
|
|
<strong>The insulin receptor and the molecular mechanism of insulin action.</strong>
|
|
J. Clin. Invest. 82: 1151-1156, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3049671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3049671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3049671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI113711" target="_blank">Full Text</a>]
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|
|
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|
|
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|
|
Leme, C. E., Wajchenberg, B. L., Lerario, A. C., Goldman, J., Borges, J. L. C.
|
|
<strong>Acanthosis nigricans, hirsutism, insulin resistance and insulin receptor defect.</strong>
|
|
Clin. Endocr. 17: 43-49, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6749340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6749340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6749340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1111/j.1365-2265.1982.tb02632.x" target="_blank">Full Text</a>]
|
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|
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|
|
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|
|
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|
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|
|
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|
|
<p class="mim-text-font">
|
|
Mariani, S., Pedone, A., Meschi, F., Di Natale, B., Caputo, R., Broggi, U., Chiumello, G.
|
|
<strong>Insulin resistance in a child with acanthosis nigricans type A.</strong>
|
|
Acta Paediat. Scand. 71: 667-670, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7136687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7136687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7136687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1111/j.1651-2227.1982.tb09496.x" target="_blank">Full Text</a>]
|
|
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|
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|
|
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|
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|
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|
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<a id="Moller1994" class="mim-anchor"></a>
|
|
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|
|
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|
|
Moller, D. E., Cohen, O., Yamaguchi, Y., Assiz, R., Grigorescu, F., Eberle, A., Morrow, L. A., Moses, A. C., Flier, J. S.
|
|
<strong>Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance.</strong>
|
|
Diabetes 43: 247-255, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8288049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8288049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8288049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.2337/diab.43.2.247" target="_blank">Full Text</a>]
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|
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|
|
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|
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|
|
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|
|
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|
|
Odawara, M., Kadowaki, T., Yamamoto, R., Shibasaki, Y., Tobe, K., Accili, D., Bevins, C., Mikami, Y., Matsuura, N., Akanuma, Y., Takaku, F., Taylor, S. I., Kasuga, M.
|
|
<strong>Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor.</strong>
|
|
Science 245: 66-68, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2544998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2544998</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2544998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.2544998" target="_blank">Full Text</a>]
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|
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|
|
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|
|
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|
|
Ojamaa, K., Hedo, J. A., Roberts, C. T., Jr., Moncada, V. Y., Gorden, P., Ullrich, A., Taylor, S. I.
|
|
<strong>Defects in human insulin receptor gene expression.</strong>
|
|
Molec. Endocr. 2: 242-247, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2840573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2840573</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2840573" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/mend-2-3-242" target="_blank">Full Text</a>]
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|
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|
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|
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Prince, M. J., Smith, F. E., Peters, E. J., Stuart, C. A.
|
|
<strong>Functional characteristics of decreased insulin receptors on fibroblasts obtained from a subject with severe insulin resistance and acanthosis nigricans.</strong>
|
|
Diabetes 35: 148-154, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3510921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3510921</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3510921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.2337/diab.35.2.148" target="_blank">Full Text</a>]
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|
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|
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Rudiger, H. W., Ahrens, P., Dreyer, M., Frorath, B., Loffel, C., Schmidt-Preuss, U.
|
|
<strong>Impaired insulin-induced RNA synthesis secondary to a genetically defective insulin receptor.</strong>
|
|
Hum. Genet. 69: 76-78, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2578425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2578425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2578425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00295533" target="_blank">Full Text</a>]
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Rudiger, H. W., Dreyer, M., Kuhnau, J., Bartelheimer, H.
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<strong>Familial insulin-resistant diabetes secondary to an affinity defect of the insulin receptor.</strong>
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Hum. Genet. 64: 407-411, 1983.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6352462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6352462</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6352462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00292378" target="_blank">Full Text</a>]
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Schwenk, W. F., Rizza, R. A., Mandarino, L. J., Gerich, J. E., Hayles, A. B., Haymond, M. W.
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<strong>Familial insulin resistance and acanthosis nigricans: presence of a postbinding defect.</strong>
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Diabetes 35: 33-37, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3510137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3510137</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3510137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.2337/diab.35.1.33" target="_blank">Full Text</a>]
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<p class="mim-text-font">
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Seemanova, E., Rudiger, H. W., Dreyer, M.
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<strong>Autosomal dominant insulin resistance syndrome due to a postbinding defect.</strong>
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Am. J. Med. Genet. 44: 705-712, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1282780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1282780</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1282780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320440602" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 3/28/2014
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Victor A. McKusick : 11/6/2006
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carol : 03/31/2014
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mcolton : 3/28/2014<br>carol : 11/6/2006
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<strong>#</strong> 610549
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DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
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INSULIN RECEPTOR, DEFECT IN, WITH INSULIN-RESISTANT DIABETES MELLITUS AND ACANTHOSIS NIGRICANS<br />
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DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS, TYPE A<br />
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IRAN, TYPE A
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<strong>SNOMEDCT:</strong> 237606005;
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<strong>ORPHA:</strong> 2297;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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19p13.2
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<span class="mim-font">
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Diabetes mellitus, insulin-resistant, with acanthosis nigricans
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<span class="mim-font">
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610549
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3
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INSR
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147670
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because insulin-resistant diabetes mellitus with acanthosis nigricans can be caused by heterozygous, homozygous, or compound heterozygous mutation in the INSR gene (147670) on chromosome 19p13.</p>
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<strong>Clinical Features</strong>
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<p>Kahn et al. (1976) divided the syndrome of insulin resistance and acanthosis nigricans into two: type A, a syndrome of younger females with signs of virilization and accelerated growth in whom a defect in cell receptors for insulin may be primary; and type B, a syndrome in older females with signs of an immunologic disease in whom circulating antibodies to the insulin receptor are found. Although no familial cases were found, they commented that all their patients and those in the literature were female; most were black, although the syndrome has been observed in persons of American Indian, Italian, Venezuelan, and Japanese origin. Despite insulin resistance, ketoacidosis was rare. Females with the type A syndrome have polycystic ovaries. </p><p>Rudiger et al. (1983) described 3 sibs with mild diabetes in combination with acanthosis nigricans and minor physical abnormalities: bitemporal narrowing of the skull, paucity of body fat, acral hypertrophy (enlarged ears, nose, chin, and finger tips), brachydactyly, protrusion of the eye globes, and dental anomalies (supernumerary teeth, severe and premature caries, abnormally prominent lower canines and upper incisors). Fasting plasma insulin was 100 times normal. Insulin-binding was defective. Scatchard analysis showed a normal number of insulin-binding sites per cell but a complete lack of insulin binding to the high-affinity receptor component. </p><p>In patients with an inherited affinity defect of the insulin receptor, Rudiger et al. (1985) found that stimulation of glucose uptake, an early effect of insulin, was normal, but insulin-mediated stimulation of RNA synthesis, a late effect, was defective. Both the affinity defect and the deficient stimulation of RNA synthesis were apparent at low concentrations of insulin only and disappeared at very high concentrations. </p><p>Mariani et al. (1982) described a 6.3-year-old girl with acanthosis nigricans, insulin-resistant diabetes mellitus, hypertelorism, prognathism, macroglossia, and large ears. Generalized hypertrichosis and hypertrophy of the clitoris were present. A decrease in the number of insulin receptors was demonstrated. In the patient reported by Leme et al. (1982), polycystic ovaries were also present. Insulin resistance with acanthosis nigricans but with normal receptors may have a postreceptor defect (Bar et al., 1978). Prince et al. (1986) studied a 15-year-old black female with menstrual irregularity, mild hirsutism, and marked acanthosis nigricans that was first noted at age 4 years. Insulin receptors on cultured fibroblasts were decreased and the remaining receptors showed a functional impairment. Perhaps one should speak of types A1 and A2 of insulin-resistance and acanthosis nigricans (IRAN), type A2 being a form with a postbinding defect. </p><p>Grigorescu et al. (1984) and Grunberger et al. (1984) described patients with type A insulin resistance and decreased insulin receptor kinase activity. In 2 patients with type A extreme insulin resistance, sisters who were the products of a consanguineous marriage, Ojamaa et al. (1988) found normal levels of insulin receptor mRNA. They had previously shown that the insulin receptor precursor is synthesized at a normal rate in these patients, thus suggesting a defect in the posttranslational processing of the receptor or in its translocation to the plasma membrane. See review by Kahn and White (1988). </p><p>Schwenk et al. (1986) observed acanthosis nigricans in a white family; the mother and 3 daughters (including a set of identical twins) had acanthosis nigricans. Three sons were normal. Two of the 4 affected females had no apparent ovarian dysfunction, whereas 2 had hyperprolactinemia without other findings of polycystic ovary disease (184700). The twins had muscle cramps (see 200170). All had normal red cell and monocyte binding of insulin. Insulin responsiveness, on the other hand, was reduced, suggesting a postbinding defect. They raised the question of autosomal dominant inheritance. </p><p>Seemanova et al. (1992) investigated a family in which at least 4 men in 3 generations had a syndrome of obesity, mild mental retardation, delayed puberty, macroorchidism, acanthosis nigricans, hyperinsulinemia, and, later, overt insulin-resistant diabetes mellitus (noninsulin-dependent diabetes mellitus, or type II diabetes). The patients had markedly curly scalp hair and deficient hair of the face and body. Teeth were normal. There was normal insulin binding to fibroblasts; however, insulin-stimulated RNA synthesis was decreased as compared to that of normal control individuals, suggesting a postbinding defect in insulin action. The pedigree showed an autosomal dominant pattern of inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>In a young Japanese male with insulin-resistant diabetes mellitus and acanthosis nigricans, Odawara et al. (1989) identified a mutation in the INSR gene (147670.0001). </p><p>Among 22 unrelated women with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (hyperandrogenemia, oligoamenorrhea, and hirsutism), Moller et al. (1994) identified only 1 mutation in the INSR gene: arg1174 to gln (147670.0030). Moller et al. (1994) concluded that mutation in the INSR gene is a rare cause of the type A syndrome of extreme insulin resistance. </p><p>Acanthosis nigricans in association with insulin resistance behaves as either a dominant (e.g., 147670.0001) or a recessive (e.g., 147670.0004). The polycystic ovary syndrome is sometimes associated. The autosomal dominant mutations in the insulin receptor gene are 'dominant negatives;' the mutant receptor protein interferes with the function of the normal receptor.</p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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Dash et al. (2009) screened 156 severely insulin-resistant patients with acanthosis nigricans for mutations in the candidate gene TBC1D4 (612465) and identified a 23-year-old woman who was heterozygous for a nonsense mutation (R363X; 612465.0001). The mutation was present in her affected half sister, as well as in their mother and a maternal aunt, neither of whom exhibited acanthosis nigricans but who did have a disproportionate rise in insulin following oral glucose load. Their maternal grandmother, who also carried the mutation, showed a normal peak-to-fasting insulin ratio but had an elevated fasting glucose and impaired glucose tolerance, indicative of significant beta-cell dysfunction. The mutation was not found in an unaffected aunt who was obese but had normal glucose tolerance and a normal peak-to-fasting insulin ratio, or in 200 ethnically matched alleles. </p>
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<strong>See Also:</strong>
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</span>
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<span class="mim-text-font">
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Grigorescu et al. (1986)
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<span class="mim-font">
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<strong>REFERENCES</strong>
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<p />
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<p class="mim-text-font">
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Bar, R. S., Muggeo, M., Roth, J., Kahn, C. R., Havrankova, J., Imperato-McGinley, J.
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<strong>Insulin resistance, acanthosis nigricans, and normal insulin receptors in a young woman: evidence for a postreceptor defect.</strong>
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J. Clin. Endocr. Metab. 47: 620-625, 1978.
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[PubMed: 400728]
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[Full Text: https://doi.org/10.1210/jcem-47-3-620]
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Dash, S., Sano, H., Rochford, J. J., Semple, R. K., Yeo, G., Hyden, C. S. S., Soos, M. A., Clark, J., Rodin, A., Langenberg, C., Druet, C., Fawcett, K. A., Tung, Y. C. L., Wareham, N. J., Barroso, I., Lienhard, G. E., O'Rahilly, S., Savage, D. B.
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<strong>A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia.</strong>
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Proc. Nat. Acad. Sci. 106: 9350-9355, 2009.
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[PubMed: 19470471]
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[Full Text: https://doi.org/10.1073/pnas.0900909106]
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Grigorescu, F., Flier, J. S., Kahn, C. R.
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<strong>Defect in insulin receptor phosphorylation in erythrocytes and fibroblasts associated with severe insulin resistance.</strong>
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J. Biol. Chem. 259: 15003-15006, 1984.
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[PubMed: 6392291]
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<p class="mim-text-font">
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Grigorescu, F., Flier, J. S., Kahn, C. R.
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<strong>Characterization of binding and phosphorylation defects of erythrocyte insulin receptors in the type A syndrome of insulin resistance.</strong>
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Diabetes 35: 127-138, 1986.
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[PubMed: 3510919]
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|
|
[Full Text: https://doi.org/10.2337/diab.35.2.127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grunberger, G., Zick, Y., Gordon, G.
|
|
<strong>Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding.</strong>
|
|
Science 223: 932-934, 1984.
|
|
|
|
|
|
[PubMed: 6141638]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.6141638]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kahn, C. R., Flier, J. S., Bar, R. S., Archer, J. A., Gorden, P., Martin, M. M., Roth, J.
|
|
<strong>The syndromes of insulin resistance and acanthosis nigricans: insulin receptor disorders in man.</strong>
|
|
New Eng. J. Med. 294: 739-745, 1976.
|
|
|
|
|
|
[PubMed: 176581]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197604012941401]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kahn, C. R., White, M. F.
|
|
<strong>The insulin receptor and the molecular mechanism of insulin action.</strong>
|
|
J. Clin. Invest. 82: 1151-1156, 1988.
|
|
|
|
|
|
[PubMed: 3049671]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI113711]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leme, C. E., Wajchenberg, B. L., Lerario, A. C., Goldman, J., Borges, J. L. C.
|
|
<strong>Acanthosis nigricans, hirsutism, insulin resistance and insulin receptor defect.</strong>
|
|
Clin. Endocr. 17: 43-49, 1982.
|
|
|
|
|
|
[PubMed: 6749340]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2265.1982.tb02632.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mariani, S., Pedone, A., Meschi, F., Di Natale, B., Caputo, R., Broggi, U., Chiumello, G.
|
|
<strong>Insulin resistance in a child with acanthosis nigricans type A.</strong>
|
|
Acta Paediat. Scand. 71: 667-670, 1982.
|
|
|
|
|
|
[PubMed: 7136687]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1651-2227.1982.tb09496.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moller, D. E., Cohen, O., Yamaguchi, Y., Assiz, R., Grigorescu, F., Eberle, A., Morrow, L. A., Moses, A. C., Flier, J. S.
|
|
<strong>Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance.</strong>
|
|
Diabetes 43: 247-255, 1994.
|
|
|
|
|
|
[PubMed: 8288049]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diab.43.2.247]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Odawara, M., Kadowaki, T., Yamamoto, R., Shibasaki, Y., Tobe, K., Accili, D., Bevins, C., Mikami, Y., Matsuura, N., Akanuma, Y., Takaku, F., Taylor, S. I., Kasuga, M.
|
|
<strong>Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor.</strong>
|
|
Science 245: 66-68, 1989.
|
|
|
|
|
|
[PubMed: 2544998]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.2544998]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ojamaa, K., Hedo, J. A., Roberts, C. T., Jr., Moncada, V. Y., Gorden, P., Ullrich, A., Taylor, S. I.
|
|
<strong>Defects in human insulin receptor gene expression.</strong>
|
|
Molec. Endocr. 2: 242-247, 1988.
|
|
|
|
|
|
[PubMed: 2840573]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/mend-2-3-242]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Prince, M. J., Smith, F. E., Peters, E. J., Stuart, C. A.
|
|
<strong>Functional characteristics of decreased insulin receptors on fibroblasts obtained from a subject with severe insulin resistance and acanthosis nigricans.</strong>
|
|
Diabetes 35: 148-154, 1986.
|
|
|
|
|
|
[PubMed: 3510921]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diab.35.2.148]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudiger, H. W., Ahrens, P., Dreyer, M., Frorath, B., Loffel, C., Schmidt-Preuss, U.
|
|
<strong>Impaired insulin-induced RNA synthesis secondary to a genetically defective insulin receptor.</strong>
|
|
Hum. Genet. 69: 76-78, 1985.
|
|
|
|
|
|
[PubMed: 2578425]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00295533]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudiger, H. W., Dreyer, M., Kuhnau, J., Bartelheimer, H.
|
|
<strong>Familial insulin-resistant diabetes secondary to an affinity defect of the insulin receptor.</strong>
|
|
Hum. Genet. 64: 407-411, 1983.
|
|
|
|
|
|
[PubMed: 6352462]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00292378]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schwenk, W. F., Rizza, R. A., Mandarino, L. J., Gerich, J. E., Hayles, A. B., Haymond, M. W.
|
|
<strong>Familial insulin resistance and acanthosis nigricans: presence of a postbinding defect.</strong>
|
|
Diabetes 35: 33-37, 1986.
|
|
|
|
|
|
[PubMed: 3510137]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diab.35.1.33]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seemanova, E., Rudiger, H. W., Dreyer, M.
|
|
<strong>Autosomal dominant insulin resistance syndrome due to a postbinding defect.</strong>
|
|
Am. J. Med. Genet. 44: 705-712, 1992.
|
|
|
|
|
|
[PubMed: 1282780]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320440602]
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