{"id":106,"date":"2023-09-29T16:00:14","date_gmt":"2023-09-29T16:00:14","guid":{"rendered":"http:\/\/sebgc.es\/blog\/?guid=353cef77b2373e92cb5e0096c266c0b5"},"modified":"2024-01-19T10:35:25","modified_gmt":"2024-01-19T10:35:25","slug":"neurofibromatosis-type-1-mosaicism-in-patients-with-constitutional-mismatch-repair-deficiency","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2023\/09\/29\/neurofibromatosis-type-1-mosaicism-in-patients-with-constitutional-mismatch-repair-deficiency\/","title":{"rendered":"Neurofibromatosis type 1 mosaicism in patients with constitutional mismatch repair deficiency"},"content":{"rendered":"\n<p>Differential diagnosis between <I>constitutional mismatch repair deficiency (CMMRD)<\/I> and <I>neurofibromatosis type 1 (NF1<\/I>) is crucial as treatment and surveillance differ. We report the case of a girl with a clinical diagnosis of sporadic NF1 who developed a glioblastoma. Immunohistochemistry for MMR proteins identified PMS2 loss in tumour and normal cells and WES showed the tumour had an ultra-hypermutated phenotype, supporting the diagnosis of CMMRD. Germline analyses identified two variants (one pathogenic variant and one classified as variant(s) of unknown significance) in the <I>PMS2<\/I> gene and subsequent functional assays on blood lymphocytes confirmed the diagnosis of CMMRD. The large plexiform neurofibroma of the thigh and the freckling were however more compatible with NF1. Indeed, a <I>NF1<\/I> PV (variant allele frequencies of 20%, 3% and 9% and in blood, skin and saliva samples, respectively) was identified confirming a mosaicism for NF1. Retrospective analysis of a French cohort identified NF1 mosaicism in blood DNA in 2 out of 22 patients with CMMRD, underlining the existence of early postzygotic PV of <I>NF1<\/I> gene in patients with CMMRD whose tumours have been frequently reported to exhibit somatic <I>NF1<\/I> mutations. It highlights the potential role of this pathway in the pathogenesis of CMMRD-associated gliomas and argues in favour of testing MEK inhibitors in this context.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Differential diagnosis between constitutional mismatch repair deficiency (CMMRD) and neurofibromatosis type 1 (NF1) is crucial as treatment and surveillance differ. We report the case of a girl with a clinical diagnosis of sporadic NF1 who developed a&#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,14,9],"tags":[],"class_list":["post-106","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg","category-open-access"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/106","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=106"}],"version-history":[{"count":2,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/106\/revisions"}],"predecessor-version":[{"id":412,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/106\/revisions\/412"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=106"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=106"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=106"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}