{"id":17799,"date":"2018-08-14T15:29:27","date_gmt":"2018-08-14T22:29:27","guid":{"rendered":"https:\/\/mr66givry2.onrocket.site\/?p=17799"},"modified":"2026-01-20T16:18:23","modified_gmt":"2026-01-21T00:18:23","slug":"fuchs-corneal-dystrophy-dm1-patients-lacking-fuchs-mutation","status":"publish","type":"post","link":"https:\/\/myotonic.org\/fr\/fuchs-corneal-dystrophy-dm1-patients-lacking-fuchs-mutation\/","title":{"rendered":"Fuchs\u2019 Corneal Dystrophy in DM1 Patients Lacking the Fuchs\u2019 Mutation"},"content":{"rendered":"

An\u00a0Ophthalmological Perspective on\u00a0DM1<\/h2>\n

When considering the spectrum of organ system involvement in DM1, the list of ophthalmological considerations is usually short\u2014cataracts being the major concern, but also ophthalmoplegia (including ptosis) and extraocular muscle myotonia (see MDF\u2019s website for a review of ocular issues in DM<\/a>). Some reports have suggested the co-occurrence of DM1 and Fuchs\u2019 endothelial corneal dystrophy (FECD), a disease, like DM1, that is linked to an expanded CTG repeat (in\u00a0TCF4<\/em>\u00a0rather than\u00a0DMPK<\/em>) and MBNL sequestration along with expanded CUG RNA in nuclear foci. Identification of this pathophysiologic mechanism link between the two diseases suggests that the RNA gain-of-function in\u00a0DMPK<\/em>\u00a0that produces DM1 may also put these patients at risk for\u00a0FECD.<\/p>\n

A\u00a0Prospective Study of DM1 Patients for\u00a0FECD<\/h2>\n

Due to the mechanistic similarities between DM1 and FECD\u2014that both are RNA gain-of-function diseases resulting from MBNL sequestration by expanded trinucleotide repeats\u2014Dr. Keith Baratz (Mayo Clinic) and colleagues prospectively evaluated 26 subjects from 14 DM1 families for phenotypic FECD and expanded repeats in\u00a0DMPK<\/em>\u00a0and\u00a0TCF4<\/em>.<\/p>\n

The research team identified five genotypically and phenotypically DM1 probands with phenotypic FECD (36%), a prevalence that greatly exceeded the prevalence of FECD in the at-risk age group in the general population (5%). Genotypic evaluation of samples available from 4 probands failed to show expanded CTG repeats in\u00a0TCF4<\/em>\u2014thus each was phenotypically FECD without the normally associated genotype\u2014but each had repeat expansions in\u00a0DMPK<\/em>. Co-segregation of DM1 and FECD was found in 12 additional family members; none of the affected individuals had expanded repeats in\u00a0TCF4<\/em>. Finally, RNASeq evaluation of RNA samples from the corneal epithelia of a FECD-affected and an unaffected subject confirmed target tissue expression of both\u00a0DMPK\u00a0<\/em>and\u00a0TCF4<\/em>.<\/p>\n

Monitor\u00a0DM1 Patients for Development of\u00a0FECD<\/h2>\n

These data suggest that DM1 patients are at risk for phenotypic FECD even though they lack the disease-causing expanded repeat in\u00a0TCF4<\/em>. Sequestration of MBNL and disruptions to alternative splicing patterns appear to be the commonality to the two diseases. Chromsomal location of the MBNL-sequestering pathogenic expanded repeat sequence then may not be essential in causation of either disease. The research group did not find an association between clinical\/genetic traits of DM1 and the presence\/severity of FECD\u2014but they acknowledge that such analyses would likely require a considerably larger cohort. Finally, since\u00a0TCF4\u00a0<\/em>is broadly expressed (including a putative role in CNS development and linkage to the neurodevelopmental disorder, Pitt-Hopkins Syndrome), the converse might be true\u2014that FECD patients are at risk for DM1\u2014but there does not appear to be any available information addressing that hypothesis, perhaps due to tissue expression levels of\u00a0TCF4<\/em>.<\/p>\n

 <\/p>\n

Reference:<\/em><\/p>\n

Fuchs’ Endothelial Corneal Dystrophy in Patients With Myotonic Dystrophy, Type 1.<\/a>
\nWinkler NS, Milone M, Martinez-Thompson JM, Raja H, Aleff RA, Patel SV, Fautsch MP, Wieben ED, Baratz KH.
\nInvest Ophthalmol Vis Sci.<\/strong>\u00a02018 Jun 1;59(7):3053-3057. doi: 10.1167\/iovs.17-23160.<\/p>\n","protected":false},"excerpt":{"rendered":"

An\u00a0Ophthalmological Perspective on\u00a0DM1 When considering the spectrum of organ system involvement in DM1, the list of ophthalmological considerations is usually short\u2014cataracts being the major concern, but also ophthalmoplegia (including ptosis) and extraocular muscle myotonia (see MDF\u2019s website for a review of ocular issues in DM). Some reports have suggested the co-occurrence of DM1 and Fuchs\u2019 […]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[72],"tags":[121],"class_list":["post-17799","post","type-post","status-publish","format-standard","hentry","category-research","tag-vision"],"_links":{"self":[{"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/posts\/17799","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/comments?post=17799"}],"version-history":[{"count":0,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/posts\/17799\/revisions"}],"wp:attachment":[{"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/media?parent=17799"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/categories?post=17799"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/tags?post=17799"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}