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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>A new molecular cause of gigantism</h1><h2>Authors</h2><ul><li>CA Stratakis</li><li>F Faucz</li><li>GP Trivellin</li></ul><h2>Abstract</h2><p>Pituitary gigantism is a rare disorder caused by growth hormone (GH)-secreting lesions. Looking for genetic defects in 46 patients with gigantism or acromegaly, we detected a novel microduplication at chromosome Xq26.3 in two unrelated kindreds and 13 sporadic cases de novo. All patients had disease onset before 5 years of age and presented with mixed GH/prolactin-secreting macroadenomas and/or hyperplasia. All sporadic cases harbored non-recurrent duplications, whereas familial cases inherited the duplications from their mothers. Breakpoint junctions revealed microhomology, suggesting a replicative mechanism for their formation. Patients shared a common duplicated region of approximately 500 Kb containing 4 genes, of which only GPR101, a G-protein coupled receptor (GPCR) that activates cAMP signaling, was consistently over-expressed in patients’ pituitary lesions. Low GPR101 expression levels were seen in non-duplicated GH-secreting tumors and in most normal adult human tissues, including the pituitary. On the contrary, high expression was observed in human fetal pituitary. In the developing zebrafish embryo a strong and brain-specific GPR101 staining was seen. We describe a new genomic disorder caused by Xq26.3 microduplications (X-LAG for X-linked Acro-Gigantism) and characterized by early-onset gigantism. This syndrome is likely caused by overexpression of GPR101, a dosage-sensitive GPCR that activates the cAMP pathway, whose mitogenic effects in pituitary somatotropes are well established. The brain is the major site of GPR101 expression across different species, especially concerning the pituitary. These differences might reflect the very different growth, development and maturation patterns among species. GPR101 may also be mutated in acromegaly of adult patients.</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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