{"id":182,"date":"2011-06-29T05:52:57","date_gmt":"2011-06-29T05:52:57","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=182"},"modified":"2026-02-25T20:57:05","modified_gmt":"2026-02-25T20:57:05","slug":"biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2011\/06\/29\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\/","title":{"rendered":"Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch-syndrome (Contributed by Monika Morak)"},"content":{"rendered":"<p>10-15% of patients suspected of Lynch-syndrome are mutation-negative in routine diagnostics. We identified the first paracentric inversion between the flanking genes <em>MLH1<\/em> and <em>LRRFIP2<\/em> flipping the genomic configuration without exonic deletion in creating two novel fusion transcripts, which even camouflaged monoallelic MLH1-deficiency when analysing only one common SNP in <em>MLH1<\/em>. Only insisting detailed analysis of the MLH1-gene deciphers the inversion, which was found in 4 family members with tumor diagnosis.<\/p>\n<p>A second case revealed a large genomic intrachromosomal duplication of the <em>MLH1 <\/em>gene region including neighbouring genes <em>TRANK1 <\/em>(<em>LBA1<\/em>) and <em>EPM2AIP1 <\/em>upstream and downstream <em>LRRFIP2 <\/em>and partially <em>GOLGA4<\/em> leaving the <em>MLH1<\/em> gene <em>per se<\/em> intact. The low-level <em>MLH1<\/em> promoter hypermethylation of 10%-25% which was found in different tissues of all three duplication carriers seems to result from the duplication, induced by a so far unknown mechanism and seems to be disease causing<\/p>\n<p>Lessons to learn: Regulatory repression might be mediated by fusion transcripts or genomic environment which implies that families highly suspicious of Lynch-Syndrome need detailed molecular testing and despite possibly negative results, thorough clinical management. (<a href=\"http:\/\/jmg.bmj.com\/content\/early\/2011\/06\/28\/jmedgenet-2011-100050.abstract?papetoc\">http:\/\/jmg.bmj.com\/content\/early\/2011\/06\/28\/jmedgenet-2011-100050.abstract?papetoc<\/a> )<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>10-15% of patients suspected of Lynch-syndrome are mutation-negative in routine diagnostics. We identified the first paracentric inversion between the flanking genes MLH1 and LRRFIP2 flipping the genomic configuration without exonic deletion in creating two novel fusion transcripts, which even camouflaged monoallelic MLH1-deficiency when analysing only one common SNP in MLH1. Only insisting detailed analysis of [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2011\/06\/29\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-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-182","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>Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch-syndrome (Contributed by Monika Morak) - 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\/2011\/06\/29\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch-syndrome (Contributed by Monika Morak) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"10-15% of patients suspected of Lynch-syndrome are mutation-negative in routine diagnostics. We identified the first paracentric inversion between the flanking genes MLH1 and LRRFIP2 flipping the genomic configuration without exonic deletion in creating two novel fusion transcripts, which even camouflaged monoallelic MLH1-deficiency when analysing only one common SNP in MLH1. Only insisting detailed analysis of [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.bmj.com\/jmg\/2011\/06\/29\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\/\" \/>\n<meta property=\"og:site_name\" content=\"JMG Contact blog\" \/>\n<meta property=\"article:published_time\" content=\"2011-06-29T05:52:57+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-25T20:57:05+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\\\/2011\\\/06\\\/29\\\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2011\\\/06\\\/29\\\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\\\/\"},\"author\":{\"name\":\"hqqu\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\"},\"headline\":\"Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch-syndrome (Contributed by Monika Morak)\",\"datePublished\":\"2011-06-29T05:52:57+00:00\",\"dateModified\":\"2026-02-25T20:57:05+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2011\\\/06\\\/29\\\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\\\/\"},\"wordCount\":207,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2011\\\/06\\\/29\\\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2011\\\/06\\\/29\\\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2011\\\/06\\\/29\\\/biallelic-mlh1-snp-cdna-expression-or-constitutional-promoter-methylation-can-hide-genomic-rearrangements-causing-lynch-syndrome\\\/\",\"name\":\"Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch-syndrome (Contributed by Monika Morak) - 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