{"id":784,"date":"2015-08-05T21:09:16","date_gmt":"2015-08-05T21:09:16","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/jmg\/?p=784"},"modified":"2015-08-05T21:09:16","modified_gmt":"2015-08-05T21:09:16","slug":"old-gene-new-phenotype-mutations-in-heparan-sulfate-synthesis-enzyme-ext2-leads-to-seizure-and-developmental-disorder-no-exostoses","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/jmg\/2015\/08\/05\/old-gene-new-phenotype-mutations-in-heparan-sulfate-synthesis-enzyme-ext2-leads-to-seizure-and-developmental-disorder-no-exostoses\/","title":{"rendered":"Old gene, new phenotype: mutations in heparan sulfate synthesis enzyme, EXT2 leads to seizure and developmental disorder, no exostoses"},"content":{"rendered":"<p>Heparan sulfate proteoglycans are essential for human development. Many genes are involved in producing heparan sulfate and when these genes are mutated, they can lead to early-onset developmental disorders affecting multiple body systems. Our group identified a family with a disease designated as seizures-scoliosis-macrocephaly syndrome, which is characterized by seizures, intellectual disability, scoliosis, and prominent head enlargement. Using next-generation sequencing, a robust genetic diagnostic tool, we identified two mutations in a heparan sulfate synthesis gene, <em>EXT2<\/em> in the patients. We used multiple approaches to assess the effect of these mutations on gene function and observed reduced EXT2 expression and activity. We have implicated a well-characterized gene in a new developmental disorder and have further illustrated the spectrum of phenotypes that can arise due to errors in heparan sulfate synthesis. (By Sali Farhan, <a href=\"http:\/\/jmg.bmj.com\/content\/early\/2015\/08\/05\/jmedgenet-2015-103279\">http:\/\/jmg.bmj.com\/content\/early\/2015\/08\/05\/jmedgenet-2015-103279<\/a> )<\/p>\n<p><a href=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/08\/2015-07-10-JMG-picture_Hegele-research-group.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-785\" src=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/08\/2015-07-10-JMG-picture_Hegele-research-group-300x195.jpg\" alt=\"2015 07 10 JMG picture_Hegele research group\" width=\"300\" height=\"195\" srcset=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/08\/2015-07-10-JMG-picture_Hegele-research-group-300x195.jpg 300w, https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/08\/2015-07-10-JMG-picture_Hegele-research-group-1024x666.jpg 1024w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><\/p>\n<p>Some of the authors (from left to right): Dr. Robert A. Hegele, John F. Robinson, Sali M.K. Farhan, and Dr. Jian Wang.<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Heparan sulfate proteoglycans are essential for human development. Many genes are involved in producing heparan sulfate and when these genes are mutated, they can lead to early-onset developmental disorders affecting multiple body systems. Our group identified a family with a disease designated as seizures-scoliosis-macrocephaly syndrome, which is characterized by seizures, intellectual disability, scoliosis, and prominent [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/jmg\/2015\/08\/05\/old-gene-new-phenotype-mutations-in-heparan-sulfate-synthesis-enzyme-ext2-leads-to-seizure-and-developmental-disorder-no-exostoses\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-784","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/784","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/comments?post=784"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/784\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/media?parent=784"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/categories?post=784"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/tags?post=784"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}