{"id":124,"date":"2023-07-06T16:00:16","date_gmt":"2023-07-06T16:00:16","guid":{"rendered":"http:\/\/sebgc.es\/blog\/?guid=a1ab6443d643ebae8168e395b669038d"},"modified":"2024-01-19T10:35:25","modified_gmt":"2024-01-19T10:35:25","slug":"mutation-in-mitral-valve-prolapse-susceptible-gene-dchs1-causes-familial-mitral-annular-disjunction","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2023\/07\/06\/mutation-in-mitral-valve-prolapse-susceptible-gene-dchs1-causes-familial-mitral-annular-disjunction\/","title":{"rendered":"Mutation in mitral valve prolapse susceptible gene DCHS1 causes familial mitral annular disjunction"},"content":{"rendered":"\n<sec><st>Background<\/st>\n<p>Mitral annular disjunction (MAD) is an under-recognised phenotype associated with severe ventricular arrhythmias. Limited knowledge has been gained on its molecular genesis.<\/p>\n<\/sec>\n<sec><st>Methods<\/st>\n<p>A total of 150 unrelated deceased Chinese were collected for whole-exome sequencing, with analysis focusing on a panel of 118 genes associated with &lsquo;abnormal mitral valve morphology&rsquo;. Cases were prespecified as &lsquo;longitudinally extensive MAD (LE-MAD)&rsquo; or &lsquo;longitudinally less-extensive MAD (LLE-MAD)&rsquo; according to the gross disjunctional length with a cut-off of 4.0 mm. The pedigree investigation was conducted on a case carrying an ultra-rare (minor allele frequency &lt;0.1%) deleterious variant in <I>DCHS1<\/I>.<\/p>\n<\/sec>\n<sec><st>Results<\/st>\n<p>Seventy-seven ultra-rare deleterious variants were finally identified. Exclusively, 12 ultra-rare deleterious variants distributed in nine genes occurred in LE-MAD, which were <I>ANK1<\/I>, <I>COL3A1<\/I>, <I>DCHS1<\/I>, <I>FBN2<\/I>, <I>GNPTAB<\/I>, <I>LZTR1<\/I>, <I>PLD1<\/I>, <I>RYR1<\/I> and <I>VPS13B<\/I>. Ultra-rare deleterious variants in those nine genes were predominantly distributed in LE-MAD compared with LLE-MAD (28% vs 5%, OR 7.30, 95% CI 2.33 to 23.38; p&lt;0.001), and the only gene related to LE-MAD with borderline significance was <I>DCHS1<\/I>. LE-MAD was consistently observed in a sizeable Chinese family, in which LE-MAD independently co-segregated with an ultra-rare deleterious variant in <I>DCHS1<\/I>, rs145429962.<\/p>\n<\/sec>\n<sec><st>Conclusion<\/st>\n<p>This study initially proposed that isolated LE-MAD might be a particular phenotype of MAD with a complex genetic predisposition. Deleterious variants in <I>DCHS1<\/I> might be associated with the morphogenesis of LE-MAD.<\/p>\n<\/sec>\n","protected":false},"excerpt":{"rendered":"<p>Background<br \/>\nMitral annular disjunction (MAD) is an under-recognised phenotype associated with severe ventricular arrhythmias. Limited knowledge has been gained on its molecular genesis.<\/p>\n<p>Methods<br \/>\nA total of 150 unrelated deceased Chinese were collected &#8230;<\/p>\n","protected":false},"author":16,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,14],"tags":[],"class_list":["post-124","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/124","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"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=124"}],"version-history":[{"count":2,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/124\/revisions"}],"predecessor-version":[{"id":416,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/124\/revisions\/416"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=124"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=124"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=124"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}