{"id":901,"date":"2016-06-22T19:24:34","date_gmt":"2016-06-22T19:24:34","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/jmg\/?p=901"},"modified":"2016-06-22T19:24:34","modified_gmt":"2016-06-22T19:24:34","slug":"identification-of-bi-alleliclrrk1mutations-inosteosclerotic-metaphyseal-dysplasiaand-evidence-for-locus-heterogeneity","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/jmg\/2016\/06\/22\/identification-of-bi-alleliclrrk1mutations-inosteosclerotic-metaphyseal-dysplasiaand-evidence-for-locus-heterogeneity\/","title":{"rendered":"Identification of bi-allelicLRRK1mutations inosteosclerotic metaphyseal dysplasiaand evidence for locus heterogeneity"},"content":{"rendered":"<p>Osteosclerotic metaphyseal dysplasia is a unique form of osteopetrosis characterized by dysplasiaof metaphyses of tubular bones with increased bone density. By exome sequencing, we found a homozygous mutation, c.5938_5944del[p.E1980Afs*66]in <em>LRRK1 <\/em>(Leucin-rich repeat kinase 1). <em>LRRK1 <\/em>was highly expressed in differentiated osteoclast. The patient\u2019s phenotype was very similar to that of <em>Lrrk1 <\/em>knockout mice that we previously reported. <em>In vitro <\/em>transfection rescue experiments using osteoclasts from the knockout mice showed that the deletion caused a loss of bone-resorbing function of osteoclast. LRRK1 can be afascinating new drug target ofosteoporosis, like RANKL and sclerostin. (By Dr. Aritoshi Iida, <a href=\"http:\/\/jmg.bmj.com\/content\/early\/2016\/04\/07\/jmedgenet-2016-103756\">http:\/\/jmg.bmj.com\/content\/early\/2016\/04\/07\/jmedgenet-2016-103756<\/a> )<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Osteosclerotic metaphyseal dysplasia is a unique form of osteopetrosis characterized by dysplasiaof metaphyses of tubular bones with increased bone density. By exome sequencing, we found a homozygous mutation, c.5938_5944del[p.E1980Afs*66]in LRRK1 (Leucin-rich repeat kinase 1). LRRK1 was highly expressed in differentiated osteoclast. The patient\u2019s phenotype was very similar to that of Lrrk1 knockout mice that we [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/jmg\/2016\/06\/22\/identification-of-bi-alleliclrrk1mutations-inosteosclerotic-metaphyseal-dysplasiaand-evidence-for-locus-heterogeneity\/\">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-901","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\/901","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=901"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/901\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/media?parent=901"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/categories?post=901"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/tags?post=901"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}