{"id":1275,"date":"2019-04-22T14:30:43","date_gmt":"2019-04-22T14:30:43","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=1275"},"modified":"2026-02-24T00:41:41","modified_gmt":"2026-02-24T00:41:41","slug":"a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2019\/04\/22\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\/","title":{"rendered":"A novel mutation in the GFAP gene expands the phenotype of Alexander disease (Contributed by Dr. Edgard Verdura)"},"content":{"rendered":"<p>We used exome sequencing to diagnose a family presenting with adult-onset spastic paraplegia. We identified a novel variant in\u00a0<em>GFAP<\/em>\u00a0(p.Gly18Val) cosegregating in multiple relatives, reaching a LOD score of 2.7. All patients showed characteristic signal changes in MRI and\u00a0abnormal MRS.\u00a0<em>In vitro<\/em>, this variant did not cause significant protein aggregation, but enlarged size of astrocytes instead, consistent with neuropathological findings in patients brain and mouse models. This suggests that alternative pathogenetic mechanisms may occur, leading to an attenuated phenotype of Alexander Disease type II in this family. We posit WES as first-tier test in adult-onset spastic paraplegias. (<a href=\"https:\/\/jmg.bmj.com\/content\/early\/2019\/04\/18\/jmedgenet-2018-105959\">https:\/\/jmg.bmj.com\/content\/early\/2019\/04\/18\/jmedgenet-2018-105959<\/a> )<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>We used exome sequencing to diagnose a family presenting with adult-onset spastic paraplegia. We identified a novel variant in\u00a0GFAP\u00a0(p.Gly18Val) cosegregating in multiple relatives, reaching a LOD score of 2.7. All patients showed characteristic signal changes in MRI and\u00a0abnormal MRS.\u00a0In vitro, this variant did not cause significant protein aggregation, but enlarged size of astrocytes instead, consistent [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2019\/04\/22\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":123,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1275","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>A novel mutation in the GFAP gene expands the phenotype of Alexander disease (Contributed by Dr. Edgard Verdura) - JMG Contact blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.bmj.com\/jmg\/2019\/04\/22\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A novel mutation in the GFAP gene expands the phenotype of Alexander disease (Contributed by Dr. Edgard Verdura) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"We used exome sequencing to diagnose a family presenting with adult-onset spastic paraplegia. We identified a novel variant in\u00a0GFAP\u00a0(p.Gly18Val) cosegregating in multiple relatives, reaching a LOD score of 2.7. All patients showed characteristic signal changes in MRI and\u00a0abnormal MRS.\u00a0In vitro, this variant did not cause significant protein aggregation, but enlarged size of astrocytes instead, consistent [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.bmj.com\/jmg\/2019\/04\/22\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\/\" \/>\n<meta property=\"og:site_name\" content=\"JMG Contact blog\" \/>\n<meta property=\"article:published_time\" content=\"2019-04-22T14:30:43+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-24T00:41:41+00:00\" \/>\n<meta name=\"author\" content=\"hqqu\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@HuiQiQu\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"hqqu\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2019\\\/04\\\/22\\\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2019\\\/04\\\/22\\\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\\\/\"},\"author\":{\"name\":\"hqqu\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\"},\"headline\":\"A novel mutation in the GFAP gene expands the phenotype of Alexander disease (Contributed by Dr. Edgard Verdura)\",\"datePublished\":\"2019-04-22T14:30:43+00:00\",\"dateModified\":\"2026-02-24T00:41:41+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2019\\\/04\\\/22\\\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\\\/\"},\"wordCount\":126,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2019\\\/04\\\/22\\\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2019\\\/04\\\/22\\\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2019\\\/04\\\/22\\\/a-novel-mutation-in-the-gfap-gene-expands-the-phenotype-of-alexander-disease\\\/\",\"name\":\"A novel mutation in the GFAP gene expands the phenotype of Alexander disease (Contributed by Dr. Edgard Verdura) - 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