{"id":2099,"date":"2025-08-20T13:47:24","date_gmt":"2025-08-20T13:47:24","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=2099"},"modified":"2026-02-22T00:54:31","modified_gmt":"2026-02-22T00:54:31","slug":"development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2025\/08\/20\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\/","title":{"rendered":"Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort (Contributed by Dr. Agn\u00e8s Desroches-Castan)"},"content":{"rendered":"<p>Hereditary Hemorrhagic Telangiectasia (HHT) and Juvenile Polyposis Syndrome (JPS) can be caused by deleterious variants in the\u00a0<em>SMAD4\u00a0<\/em>gene, which is part of the TGF\u00df\/BMP signaling pathway. We developed a functional assay for SMAD4 variants that\u00a0allows discrimination between benign and pathogenic\u00a0<em>SMAD4<\/em> variants. We found that all the variants tested led to a loss of function in the SMAD4 protein. Most of these variants impaired SMAD4 association with other SMAD proteins. This assay will be transferable to clinical genetic laboratories and will improve the diagnosis of HHT-JPS patients. (<a href=\"https:\/\/jmg.bmj.com\/content\/early\/2025\/08\/19\/jmg-2025-110797\">https:\/\/jmg.bmj.com\/content\/early\/2025\/08\/19\/jmg-2025-110797<\/a> )<\/p>\n<p>&nbsp;<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Hereditary Hemorrhagic Telangiectasia (HHT) and Juvenile Polyposis Syndrome (JPS) can be caused by deleterious variants in the\u00a0SMAD4\u00a0gene, which is part of the TGF\u00df\/BMP signaling pathway. We developed a functional assay for SMAD4 variants that\u00a0allows discrimination between benign and pathogenic\u00a0SMAD4 variants. We found that all the variants tested led to a loss of function in the [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2025\/08\/20\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\/\">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-2099","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort (Contributed by Dr. Agn\u00e8s Desroches-Castan) - 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\/2025\/08\/20\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort (Contributed by Dr. Agn\u00e8s Desroches-Castan) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"Hereditary Hemorrhagic Telangiectasia (HHT) and Juvenile Polyposis Syndrome (JPS) can be caused by deleterious variants in the\u00a0SMAD4\u00a0gene, which is part of the TGF\u00df\/BMP signaling pathway. We developed a functional assay for SMAD4 variants that\u00a0allows discrimination between benign and pathogenic\u00a0SMAD4 variants. We found that all the variants tested led to a loss of function in the [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.bmj.com\/jmg\/2025\/08\/20\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\/\" \/>\n<meta property=\"og:site_name\" content=\"JMG Contact blog\" \/>\n<meta property=\"article:published_time\" content=\"2025-08-20T13:47:24+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-22T00:54:31+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\\\/2025\\\/08\\\/20\\\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2025\\\/08\\\/20\\\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\\\/\"},\"author\":{\"name\":\"hqqu\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\"},\"headline\":\"Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort (Contributed by Dr. Agn\u00e8s Desroches-Castan)\",\"datePublished\":\"2025-08-20T13:47:24+00:00\",\"dateModified\":\"2026-02-22T00:54:31+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2025\\\/08\\\/20\\\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\\\/\"},\"wordCount\":123,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2025\\\/08\\\/20\\\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2025\\\/08\\\/20\\\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2025\\\/08\\\/20\\\/development-of-a-functional-assay-for-the-characterisation-of-smad4-variants-from-the-french-haemorrhagic-hereditary-telangiectasia-cohort\\\/\",\"name\":\"Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort (Contributed by Dr. Agn\u00e8s Desroches-Castan) - 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