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<title>Mutations in MGAT5B affect the complex N-linked glycans in a patient with a neuromuscular phenotye | NIH Research Festival</title>
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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>Mutations in MGAT5B affect the complex N-linked glycans in a patient with a neuromuscular phenotye</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-18">Friday, September 18, 2015</time>
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– Poster Session IV
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">12:00 – 1:30 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NHGRI</strong></p></div><div class="schedule__description"><p><strong>GEN-20</strong></p></div></div></div></div><h2>Authors</h2><ul><li>IJ Hardee</li><li>ME Hackbarth</li><li>M Davids</li><li>MS Kane</li><li>M Hee</li><li>WA Gahl</li></ul><h2>Abstract</h2><p>The NIH Undiagnosed Diseases Program (UDP) concentrates its efforts on the most puzzling medical cases, focusing on disease discovery and patient diagnosis using both genomic data and basic research. Congenital Disorders of Glycosylation (CDGs) are a group of disorders whose phenotypes lack consistent clinical features or biomarkers, and are difficult to diagnose. For one of the patients in the UDP a homozygous biallelic mutation in Mannosyl (Alpha-1,6-)-Glycoprotein Beta-1,6-N-Acetyl-Glucosaminyltransferase, Isozyme B (MGAT5B; NM_198955.1:c.1256C>T) that results in p.Thr419Met was discovered using whole exome sequencing. The MGAT5B gene encodes a N-acetylglucosaminyl-transferase that acts on alpha-linked mannose of N-linked glycans in the synthesis of complex cell surface N-glycans. Additionally it can act on the GlcNAcbeta1,2-Manalpha1-Ser/Thr moiety forming branched structures in the O-mannosyl glycans. Compared to its isoform MGAT5 that is expressed ubiquitously throughout different tissues, MGAT5B is expressed exclusively in high levels in neuronal tissue. Our patient presented with a middle age onset of muscular weakness and impaired tactile sensation. Upon further examination the neuromuscular phenotype was expanded with muscle atrophy, muscle weakness, reduced tendon reflex, decreased muscle mass, dysarythria, and tongue fasiculations and atrophy. Consistent with the gene of interest, glycosylation profiles in both plasma and fibroblasts show undergalactosylation of the complex N-linked glycans. Further analysis of this candidate gene in our patient and its effect on glycosylation will be discussed.</p><p><strong>Scientific Focus Area</strong>: Genetics and Genomics</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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