{"id":912,"date":"2016-08-11T00:15:41","date_gmt":"2016-08-11T00:15:41","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=912"},"modified":"2026-02-24T21:23:53","modified_gmt":"2026-02-24T21:23:53","slug":"phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/","title":{"rendered":"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards)"},"content":{"rendered":"<p><span style=\"font-family: 'Arial',sans-serif\"><span style=\"color: #000000\">The gene <\/span><i><span style=\"color: #000000\">POLR3B<\/span><\/i><span style=\"color: #000000\"> is associated with 4H leukodystrophy, a syndrome that includes reproductive failure (in the form of idiopathic hypogonadotropic hypogonadism (IHH)), neurologic disease (often in the form of ataxia), and hypodontia. To date, most patients reported to carry biallelic variants in <\/span><i><span style=\"color: #000000\">POLR3B<\/span><\/i><span style=\"color: #000000\"> begin to show neurologic symptoms in early childhood, often before they are 3 years old. In our cohort of 565 patients with IHH, we identified four individuals with two variants in <\/span><i><span style=\"color: #000000\">POLR3B<\/span><\/i><span style=\"color: #000000\">; however, these patients were not found to have any signs of neurodegeneration or ataxia when evaluated in their early 30s. Our finding broadens the understanding of the spectrum of reproductive and neurologic disorders associated with <\/span><i><span style=\"color: #000000\">POLR3B<\/span><\/i><span style=\"color: #000000\"> mutations. (<\/span><a href=\"http:\/\/jmg.bmj.com\/content\/early\/2016\/08\/10\/jmedgenet-2016-104064\"><span style=\"color: #0563c1\">http:\/\/jmg.bmj.com\/content\/early\/2016\/08\/10\/jmedgenet-2016-104064<\/span><\/a><span style=\"color: #000000\"> )<\/span><\/span><!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The gene POLR3B is associated with 4H leukodystrophy, a syndrome that includes reproductive failure (in the form of idiopathic hypogonadotropic hypogonadism (IHH)), neurologic disease (often in the form of ataxia), and hypodontia. To date, most patients reported to carry biallelic variants in POLR3B begin to show neurologic symptoms in early childhood, often before they are [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/\">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-912","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>Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards) - 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\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"The gene POLR3B is associated with 4H leukodystrophy, a syndrome that includes reproductive failure (in the form of idiopathic hypogonadotropic hypogonadism (IHH)), neurologic disease (often in the form of ataxia), and hypodontia. To date, most patients reported to carry biallelic variants in POLR3B begin to show neurologic symptoms in early childhood, often before they are [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/\" \/>\n<meta property=\"og:site_name\" content=\"JMG Contact blog\" \/>\n<meta property=\"article:published_time\" content=\"2016-08-11T00:15:41+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-24T21:23:53+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\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/\"},\"author\":{\"name\":\"hqqu\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\"},\"headline\":\"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards)\",\"datePublished\":\"2016-08-11T00:15:41+00:00\",\"dateModified\":\"2026-02-24T21:23:53+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/\"},\"wordCount\":140,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/\",\"name\":\"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards) - JMG Contact blog\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#website\"},\"datePublished\":\"2016-08-11T00:15:41+00:00\",\"dateModified\":\"2026-02-24T21:23:53+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2016\\\/08\\\/11\\\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards)\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#website\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/\",\"name\":\"JMG Contact blog\",\"description\":\"JMG Contact blog\",\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\",\"name\":\"JMG Contact blog\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/files\\\/2017\\\/10\\\/blog-logo-jmg.png\",\"contentUrl\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/files\\\/2017\\\/10\\\/blog-logo-jmg.png\",\"width\":300,\"height\":34,\"caption\":\"JMG Contact blog\"},\"image\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/logo\\\/image\\\/\"}},{\"@type\":\"Person\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\",\"name\":\"hqqu\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/920bc4e81500cde88def4bfd7775029cb154e422c5460b9cf80d5c47137d6f35?s=96&d=mm&r=g\",\"url\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/920bc4e81500cde88def4bfd7775029cb154e422c5460b9cf80d5c47137d6f35?s=96&d=mm&r=g\",\"contentUrl\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/920bc4e81500cde88def4bfd7775029cb154e422c5460b9cf80d5c47137d6f35?s=96&d=mm&r=g\",\"caption\":\"hqqu\"},\"description\":\"Huiqi Qu has a background as a physician trained in internal medicine and a PhD in Experimental Medicine (Endocrinology). His research applies human genetics and multi-omics to complex and pediatric diseases, including GWAS, polygenic risk scores (PRS), single-cell transcriptomics, and integrative genomics to support precision medicine and clinical translation.\",\"sameAs\":[\"https:\\\/\\\/x.com\\\/HuiQiQu\"],\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/author\\\/hqiqu\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards) - JMG Contact blog","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/","og_locale":"en_US","og_type":"article","og_title":"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards) - JMG Contact blog","og_description":"The gene POLR3B is associated with 4H leukodystrophy, a syndrome that includes reproductive failure (in the form of idiopathic hypogonadotropic hypogonadism (IHH)), neurologic disease (often in the form of ataxia), and hypodontia. To date, most patients reported to carry biallelic variants in POLR3B begin to show neurologic symptoms in early childhood, often before they are [...]Read More...","og_url":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/","og_site_name":"JMG Contact blog","article_published_time":"2016-08-11T00:15:41+00:00","article_modified_time":"2026-02-24T21:23:53+00:00","author":"hqqu","twitter_card":"summary_large_image","twitter_creator":"@HuiQiQu","twitter_misc":{"Written by":"hqqu","Est. reading time":"1 minute"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/#article","isPartOf":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/"},"author":{"name":"hqqu","@id":"https:\/\/blogs.bmj.com\/jmg\/#\/schema\/person\/be0250f8d5b52412c3e7c222dabd591b"},"headline":"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards)","datePublished":"2016-08-11T00:15:41+00:00","dateModified":"2026-02-24T21:23:53+00:00","mainEntityOfPage":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/"},"wordCount":140,"commentCount":0,"publisher":{"@id":"https:\/\/blogs.bmj.com\/jmg\/#organization"},"inLanguage":"en-US","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/#respond"]}]},{"@type":"WebPage","@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/","url":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/","name":"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards) - JMG Contact blog","isPartOf":{"@id":"https:\/\/blogs.bmj.com\/jmg\/#website"},"datePublished":"2016-08-11T00:15:41+00:00","dateModified":"2026-02-24T21:23:53+00:00","breadcrumb":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/blogs.bmj.com\/jmg\/2016\/08\/11\/phenotypic-spectrum-of-polr3b-mutations-isolated-hypogonadotropic-hypogonadism-without-neurological-or-dental-anomalies\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/blogs.bmj.com\/jmg\/"},{"@type":"ListItem","position":2,"name":"Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies (Contributed by Mary Richards)"}]},{"@type":"WebSite","@id":"https:\/\/blogs.bmj.com\/jmg\/#website","url":"https:\/\/blogs.bmj.com\/jmg\/","name":"JMG Contact blog","description":"JMG Contact blog","publisher":{"@id":"https:\/\/blogs.bmj.com\/jmg\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/blogs.bmj.com\/jmg\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Organization","@id":"https:\/\/blogs.bmj.com\/jmg\/#organization","name":"JMG Contact blog","url":"https:\/\/blogs.bmj.com\/jmg\/","logo":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/blogs.bmj.com\/jmg\/#\/schema\/logo\/image\/","url":"https:\/\/blogs.bmj.com\/jmg\/files\/2017\/10\/blog-logo-jmg.png","contentUrl":"https:\/\/blogs.bmj.com\/jmg\/files\/2017\/10\/blog-logo-jmg.png","width":300,"height":34,"caption":"JMG Contact blog"},"image":{"@id":"https:\/\/blogs.bmj.com\/jmg\/#\/schema\/logo\/image\/"}},{"@type":"Person","@id":"https:\/\/blogs.bmj.com\/jmg\/#\/schema\/person\/be0250f8d5b52412c3e7c222dabd591b","name":"hqqu","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/secure.gravatar.com\/avatar\/920bc4e81500cde88def4bfd7775029cb154e422c5460b9cf80d5c47137d6f35?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/920bc4e81500cde88def4bfd7775029cb154e422c5460b9cf80d5c47137d6f35?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/920bc4e81500cde88def4bfd7775029cb154e422c5460b9cf80d5c47137d6f35?s=96&d=mm&r=g","caption":"hqqu"},"description":"Huiqi Qu has a background as a physician trained in internal medicine and a PhD in Experimental Medicine (Endocrinology). His research applies human genetics and multi-omics to complex and pediatric diseases, including GWAS, polygenic risk scores (PRS), single-cell transcriptomics, and integrative genomics to support precision medicine and clinical translation.","sameAs":["https:\/\/x.com\/HuiQiQu"],"url":"https:\/\/blogs.bmj.com\/jmg\/author\/hqiqu\/"}]}},"_links":{"self":[{"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/912","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/users\/123"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/comments?post=912"}],"version-history":[{"count":0,"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/912\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/media?parent=912"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/categories?post=912"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/tags?post=912"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}