{"id":742,"date":"2015-03-10T04:51:52","date_gmt":"2015-03-10T04:51:52","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/jmg\/?p=742"},"modified":"2015-03-10T04:51:52","modified_gmt":"2015-03-10T04:51:52","slug":"familial-periventricular-nodular-heterotopia-epilepsy-and-melnick-needles-syndrome-caused-by-a-single-flna-mutation-with-combined-gain-of-function-and-loss-of-function-effects","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/jmg\/2015\/03\/10\/familial-periventricular-nodular-heterotopia-epilepsy-and-melnick-needles-syndrome-caused-by-a-single-flna-mutation-with-combined-gain-of-function-and-loss-of-function-effects\/","title":{"rendered":"Familial periventricular nodular heterotopia, epilepsy and Melnick-Needles Syndrome caused by a single FLNA mutation with combined gain-of-function and loss-of-function effects"},"content":{"rendered":"<p>Loss-of-function mutations of the <em>FLNA<\/em> gene cause X-linked periventricular nodular heterotopia (PNH) while gain-of-function mutations cause the Otopalatodigital (OPD) spectrum. These two conditions are known to be mutually exclusive phenotypes. We describe a family in which a woman and her three daughters exhibited a phenotype combining PNH, epilepsy and Melnick-Needles syndrome, a skeletal disorder assigned to the OPD spectrum. All affected individuals harbored a novel non-conservative missense mutation in <em>FLNA<\/em> leading to two aberrant transcripts, one of which carries the missense mutation, plus a longer transcript resulting from intron 3 retention. Co-occurring gain-of and loss-of-function appears to cause the dual phenotype. (By Elena Parrini, <a href=\"http:\/\/jmg.bmj.com\/content\/early\/2015\/03\/09\/jmedgenet-2014-102959\">http:\/\/jmg.bmj.com\/content\/early\/2015\/03\/09\/jmedgenet-2014-102959<\/a> )<a href=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/03\/DSC_0114.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-743\" src=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/03\/DSC_0114-300x150.jpg\" alt=\"DSC_0114\" width=\"300\" height=\"150\" srcset=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/03\/DSC_0114-300x150.jpg 300w, https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/03\/DSC_0114-1024x512.jpg 1024w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Loss-of-function mutations of the FLNA gene cause X-linked periventricular nodular heterotopia (PNH) while gain-of-function mutations cause the Otopalatodigital (OPD) spectrum. These two conditions are known to be mutually exclusive phenotypes. We describe a family in which a woman and her three daughters exhibited a phenotype combining PNH, epilepsy and Melnick-Needles syndrome, a skeletal disorder assigned [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/jmg\/2015\/03\/10\/familial-periventricular-nodular-heterotopia-epilepsy-and-melnick-needles-syndrome-caused-by-a-single-flna-mutation-with-combined-gain-of-function-and-loss-of-function-effects\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-742","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/742","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/comments?post=742"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/742\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/media?parent=742"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/categories?post=742"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/tags?post=742"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}