{"id":1573,"date":"2020-11-12T14:53:38","date_gmt":"2020-11-12T14:53:38","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=1573"},"modified":"2026-02-23T23:26:44","modified_gmt":"2026-02-23T23:26:44","slug":"inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/","title":{"rendered":"Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome (Contributed by Pasquelena De Nittis)"},"content":{"rendered":"<p>IDDCA (MIM #617173) is an ultra-rare autosomal recessive disorder caused by mutations in <em>GNB5<\/em> gene. Genotype-phenotype correlation shows that homozygous or compound heterozygous missense variants are associated with an attenuated phenotype with mild intellectual disability (ID) and sinus node dysfunction, while homozygous null alleles cause severe ID with absent speech, epileptic encephalopathy, hypotonia and sinus node dysfunction. In this study, we investigated the cardiac dysfunction in a <em>Gnb5<\/em> knock-out mouse models of IDDCA for the first time and identified, in parallel, additional affected individuals harbouring novel pathogenic variants. Using blockade or stimulation of the parasympathetic and sympathetic systems we propose a mechanism underlying cardiac dysfunction in patients, namely impaired parasympathetic control of the heart. \u00a0(<a href=\"https:\/\/jmg.bmj.com\/content\/early\/2020\/11\/09\/jmedgenet-2020-107015\">https:\/\/jmg.bmj.com\/content\/early\/2020\/11\/09\/jmedgenet-2020-107015<\/a> )<\/p>\n<p><a href=\"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/untitled-38\/\" rel=\"attachment wp-att-1574\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-1574\" src=\"https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled-300x209.png\" alt=\"\" width=\"300\" height=\"209\" srcset=\"https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled-300x209.png 300w, https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled-1024x714.png 1024w, https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled-768x536.png 768w, https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled-640x446.png 640w, https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled.png 1458w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>IDDCA (MIM #617173) is an ultra-rare autosomal recessive disorder caused by mutations in GNB5 gene. Genotype-phenotype correlation shows that homozygous or compound heterozygous missense variants are associated with an attenuated phenotype with mild intellectual disability (ID) and sinus node dysfunction, while homozygous null alleles cause severe ID with absent speech, epileptic encephalopathy, hypotonia and sinus [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/\">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-1573","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome (Contributed by Pasquelena De Nittis) - 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\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome (Contributed by Pasquelena De Nittis) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"IDDCA (MIM #617173) is an ultra-rare autosomal recessive disorder caused by mutations in GNB5 gene. Genotype-phenotype correlation shows that homozygous or compound heterozygous missense variants are associated with an attenuated phenotype with mild intellectual disability (ID) and sinus node dysfunction, while homozygous null alleles cause severe ID with absent speech, epileptic encephalopathy, hypotonia and sinus [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/\" \/>\n<meta property=\"og:site_name\" content=\"JMG Contact blog\" \/>\n<meta property=\"article:published_time\" content=\"2020-11-12T14:53:38+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-23T23:26:44+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled.png\" \/>\n\t<meta property=\"og:image:width\" content=\"1458\" \/>\n\t<meta property=\"og:image:height\" content=\"1017\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\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\\\/2020\\\/11\\\/12\\\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2020\\\/11\\\/12\\\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\\\/\"},\"author\":{\"name\":\"hqqu\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\"},\"headline\":\"Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome (Contributed by Pasquelena De Nittis)\",\"datePublished\":\"2020-11-12T14:53:38+00:00\",\"dateModified\":\"2026-02-23T23:26:44+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2020\\\/11\\\/12\\\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\\\/\"},\"wordCount\":142,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2020\\\/11\\\/12\\\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/files\\\/2020\\\/11\\\/Untitled-300x209.png\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2020\\\/11\\\/12\\\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2020\\\/11\\\/12\\\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2020\\\/11\\\/12\\\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\\\/\",\"name\":\"Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome (Contributed by Pasquelena De Nittis) - 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Genotype-phenotype correlation shows that homozygous or compound heterozygous missense variants are associated with an attenuated phenotype with mild intellectual disability (ID) and sinus node dysfunction, while homozygous null alleles cause severe ID with absent speech, epileptic encephalopathy, hypotonia and sinus [...]Read More...","og_url":"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/","og_site_name":"JMG Contact blog","article_published_time":"2020-11-12T14:53:38+00:00","article_modified_time":"2026-02-23T23:26:44+00:00","og_image":[{"width":1458,"height":1017,"url":"https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled.png","type":"image\/png"}],"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\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/#article","isPartOf":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/"},"author":{"name":"hqqu","@id":"https:\/\/blogs.bmj.com\/jmg\/#\/schema\/person\/be0250f8d5b52412c3e7c222dabd591b"},"headline":"Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome (Contributed by Pasquelena De Nittis)","datePublished":"2020-11-12T14:53:38+00:00","dateModified":"2026-02-23T23:26:44+00:00","mainEntityOfPage":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/"},"wordCount":142,"commentCount":0,"publisher":{"@id":"https:\/\/blogs.bmj.com\/jmg\/#organization"},"image":{"@id":"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/#primaryimage"},"thumbnailUrl":"https:\/\/blogs.bmj.com\/jmg\/files\/2020\/11\/Untitled-300x209.png","inLanguage":"en-US","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/#respond"]}]},{"@type":"WebPage","@id":"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/","url":"https:\/\/blogs.bmj.com\/jmg\/2020\/11\/12\/inhibition-of-g-protein-signaling-in-cardiac-dysfunction-of-intellectual-developmental-disorder-with-cardiac-arrhythmia-iddca-syndrome\/","name":"Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome (Contributed by Pasquelena De Nittis) - 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