{"id":1761,"date":"2022-09-20T13:49:43","date_gmt":"2022-09-20T13:49:43","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=1761"},"modified":"2026-02-23T00:44:40","modified_gmt":"2026-02-23T00:44:40","slug":"clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2022\/09\/20\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\/","title":{"rendered":"Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome (Contributed by Dr. Shiomi Otsuji)"},"content":{"rendered":"<p>The Retriever subunit VPS35L is the third responsible gene for Ritscher-Schinzel syndrome (RSS) after WASHC5 and CCDC22. To date, only one pair of siblings have been reported and their condition was significantly more severe than typical RSS. This report expands the clinical spectrum of patients with pathogenic VPS35L variants, and identifies both overlapping and distinctive features compared with patients with CCC and WASH complex dysfunction. We also demonstrate a possible molecular mechanism for aberrant lipid metabolism observed in these patients. This study contributes to the establishment of a disease concept for VPS35L-associated RSS. (<a href=\"https:\/\/jmg.bmj.com\/content\/early\/2022\/09\/15\/jmg-2022-108602\">https:\/\/jmg.bmj.com\/content\/early\/2022\/09\/15\/jmg-2022-108602<\/a> )<\/p>\n<p><a href=\"https:\/\/blogs.bmj.com\/jmg\/2022\/09\/20\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\/untitled-59\/\" rel=\"attachment wp-att-1762\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-1762\" src=\"https:\/\/blogs.bmj.com\/jmg\/files\/2022\/09\/Untitled-300x197.png\" alt=\"\" width=\"300\" height=\"197\" srcset=\"https:\/\/blogs.bmj.com\/jmg\/files\/2022\/09\/Untitled-300x197.png 300w, https:\/\/blogs.bmj.com\/jmg\/files\/2022\/09\/Untitled-1024x673.png 1024w, https:\/\/blogs.bmj.com\/jmg\/files\/2022\/09\/Untitled-768x505.png 768w, https:\/\/blogs.bmj.com\/jmg\/files\/2022\/09\/Untitled-1536x1010.png 1536w, https:\/\/blogs.bmj.com\/jmg\/files\/2022\/09\/Untitled-640x421.png 640w, https:\/\/blogs.bmj.com\/jmg\/files\/2022\/09\/Untitled.png 1601w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The Retriever subunit VPS35L is the third responsible gene for Ritscher-Schinzel syndrome (RSS) after WASHC5 and CCDC22. To date, only one pair of siblings have been reported and their condition was significantly more severe than typical RSS. This report expands the clinical spectrum of patients with pathogenic VPS35L variants, and identifies both overlapping and distinctive [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2022\/09\/20\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-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-1761","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>Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome (Contributed by Dr. Shiomi Otsuji) - 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\/2022\/09\/20\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome (Contributed by Dr. Shiomi Otsuji) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"The Retriever subunit VPS35L is the third responsible gene for Ritscher-Schinzel syndrome (RSS) after WASHC5 and CCDC22. To date, only one pair of siblings have been reported and their condition was significantly more severe than typical RSS. This report expands the clinical spectrum of patients with pathogenic VPS35L variants, and identifies both overlapping and distinctive [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.bmj.com\/jmg\/2022\/09\/20\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\/\" \/>\n<meta property=\"og:site_name\" content=\"JMG Contact blog\" \/>\n<meta property=\"article:published_time\" content=\"2022-09-20T13:49:43+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-23T00:44:40+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/blogs.bmj.com\/jmg\/files\/2022\/09\/Untitled.png\" \/>\n\t<meta property=\"og:image:width\" content=\"1601\" \/>\n\t<meta property=\"og:image:height\" content=\"1053\" \/>\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\\\/2022\\\/09\\\/20\\\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2022\\\/09\\\/20\\\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\\\/\"},\"author\":{\"name\":\"hqqu\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\"},\"headline\":\"Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome (Contributed by Dr. Shiomi Otsuji)\",\"datePublished\":\"2022-09-20T13:49:43+00:00\",\"dateModified\":\"2026-02-23T00:44:40+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2022\\\/09\\\/20\\\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\\\/\"},\"wordCount\":119,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2022\\\/09\\\/20\\\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/files\\\/2022\\\/09\\\/Untitled-300x197.png\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2022\\\/09\\\/20\\\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2022\\\/09\\\/20\\\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2022\\\/09\\\/20\\\/clinical-diversity-and-molecular-mechanism-of-vps35l-associated-ritscher-schinzel-syndrome\\\/\",\"name\":\"Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome (Contributed by Dr. Shiomi Otsuji) - 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