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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2010-08-23T00:00:00-04:00" class="date-display-single">August 23, 2010</span></p><div class='syndicate'><h1>Kabuki Syndrome Gene Identified</h1><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2010/20100823-kabuki.jpg?itok=e3UhD4nj&timestamp=1433962575" alt="Image of a gloved hand holding a test tube" title="Image of a gloved hand holding a test tube" />
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</div><p>Scientists discovered genetic variants that account for most cases of Kabuki syndrome, a rare disorder that causes multiple birth defects and mental retardation. The finding validates the use of a rapid and less expensive DNA sequencing strategy called exome sequencing.</p>
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<p>Kabuki syndrome was originally described by Japanese scientists in 1981. Patients with the disorder often have distinct facial features that resemble the makeup worn by actors of Kabuki, a Japanese theatrical form. The syndrome also brings cardiac problems, skeletal abnormalities, immunological defects and mild to moderate mental retardation. Some inherited cases suggested that Kabuki syndrome may be caused by genetic factors. However, researchers had been unable to pinpoint the genes involved.</p>
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<p>A group of scientists at the University of Washington in Seattle recently showed that isolating and sequencing exons, rather than the entire genome, can yield important genetic information about a person quickly and at lower cost then whole genome sequencing. Exons are the parts of genome that contain the information needed to produce proteins, the building blocks of the body. The complete set of exons, the exome, makes up just a small fraction of the human genome—about 1%.</p>
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<p>In the new study, the team—led by Dr. Michael Bamshad and Dr. Jay Shendure—sequenced the exomes of 10 unrelated people with Kabuki syndrome. The researchers compared the exomes of the 10 patients to the human genome sequence to look for differences associated with the syndrome. Their work was funded by NIH's National Human Genome Research Institute (NHGRI), National Heart, Lung and Blood Institute (NHLBI) and others. The results appeared on August 15, 2010, in the advanced online edition of <em>Nature Genetics</em>.</p>
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<p>The researchers found no differences that were shared by all 10 people with Kabuki syndrome. They were able to identify several candidate genes, however, by conducting a less stringent analysis, looking for variants shared among subsets of the patients. They categorized each Kabuki case based on the patients' facial characteristics and the presence of developmental delay and/or major birth defects. They then categorized the functional impact of each newly identified genetic variant.</p>
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<p>This combined analysis pointed to a gene called <em>MLL2</em>. The protein encoded by <em>MLL2</em> is important for regulating how DNA and associated proteins are packed into chromosomes. Changes in this structure can affect DNA replication and gene expression. The variants in <em>MLL2</em> resulted in the production of a shortened, nonfunctional protein.</p>
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<p>To validate their finding, the researchers sequenced <em>MLL2</em> in 43 additional cases. In total, they found 33 distinct <em>MLL2</em> mutations in 35 of the 53 families (66%).</p>
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<p>"Our findings strongly suggest that alterations in the <em>MLL2</em> gene are a major cause of Kabuki syndrome," says Shendure.</p>
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<p>"It is clear that there may be additional genes in which variants cause Kabuki syndrome, as approximately one-third of cases did not have <em>MLL2</em> mutations," Bamshad adds. "To find these, it will be important to sequence the exomes of additional, well-characterized cases of Kabuki syndrome in which we don’t see <em>MLL2</em> mutations."</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="http://www.genome.gov/10000409" target="_top">Genetic and Rare Diseases Information Center (GARD)</a></li><li><a href="http://www.nih.gov/researchmatters/august2009/08312009exomes.htm" target="_top">Researchers Find Value in Exomes</a></li><li><a href="https://www.youtube.com/watch?v=-Qr5ahk1HEI" target="_top">Exome Sequencing (video)</a></li></ul>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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