{"id":1627,"date":"2021-04-27T00:23:14","date_gmt":"2021-04-27T00:23:14","guid":{"rendered":"https:\/\/blogs.bmj.com\/jmg\/?p=1627"},"modified":"2026-02-23T22:57:30","modified_gmt":"2026-02-23T22:57:30","slug":"haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/jmg\/2021\/04\/27\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\/","title":{"rendered":"Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice (Contributed by Prof. Feng Zhang and Prof. Yanhua Wu)"},"content":{"rendered":"<p>Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. By utilizing whole-exome sequencing, we identified a rare heterozygous loss-of-function variant of non-homologous end joining factor 1 (<em>NHEJ1<\/em>) co-segregating with POI in a three-generation Chinese family. The loss-of-function variant caused an approximately 50% reduction in NHEJ1 protein amount in human. Knock-down of <em>NHEJ1<\/em> in KGN ovarian cells significantly impaired DNA repair capacity. By constructing a knock-in mouse model, we found that haploinsufficiency of <em>Nhej1 <\/em>lead to reduced number of follicles in ovaries and impaired female fertility. Our studies provided novel insights into genetic counseling and clinical prevention of POI. (<a href=\"https:\/\/jmg.bmj.com\/content\/early\/2021\/04\/21\/jmedgenet-2020-107398\">https:\/\/jmg.bmj.com\/content\/early\/2021\/04\/21\/jmedgenet-2020-107398<\/a> )<\/p>\n<p><a href=\"https:\/\/blogs.bmj.com\/jmg\/2021\/04\/27\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\/untitled-45\/\" rel=\"attachment wp-att-1628\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-1628\" src=\"https:\/\/blogs.bmj.com\/jmg\/files\/2021\/04\/Untitled-1-300x234.png\" alt=\"\" width=\"300\" height=\"234\" srcset=\"https:\/\/blogs.bmj.com\/jmg\/files\/2021\/04\/Untitled-1-300x234.png 300w, https:\/\/blogs.bmj.com\/jmg\/files\/2021\/04\/Untitled-1-1024x798.png 1024w, https:\/\/blogs.bmj.com\/jmg\/files\/2021\/04\/Untitled-1-768x598.png 768w, https:\/\/blogs.bmj.com\/jmg\/files\/2021\/04\/Untitled-1-1536x1197.png 1536w, https:\/\/blogs.bmj.com\/jmg\/files\/2021\/04\/Untitled-1-640x499.png 640w, https:\/\/blogs.bmj.com\/jmg\/files\/2021\/04\/Untitled-1.png 1920w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. By utilizing whole-exome sequencing, we identified a rare heterozygous loss-of-function variant of non-homologous end joining factor 1 (NHEJ1) co-segregating with POI in a three-generation Chinese family. The loss-of-function variant caused an approximately 50% reduction in NHEJ1 protein amount [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/jmg\/2021\/04\/27\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":123,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1627","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice (Contributed by Prof. Feng Zhang and Prof. Yanhua Wu) - JMG Contact blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.bmj.com\/jmg\/2021\/04\/27\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice (Contributed by Prof. Feng Zhang and Prof. Yanhua Wu) - JMG Contact blog\" \/>\n<meta property=\"og:description\" content=\"Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. By utilizing whole-exome sequencing, we identified a rare heterozygous loss-of-function variant of non-homologous end joining factor 1 (NHEJ1) co-segregating with POI in a three-generation Chinese family. The loss-of-function variant caused an approximately 50% reduction in NHEJ1 protein amount [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.bmj.com\/jmg\/2021\/04\/27\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\/\" \/>\n<meta property=\"og:site_name\" content=\"JMG Contact blog\" \/>\n<meta property=\"article:published_time\" content=\"2021-04-27T00:23:14+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-23T22:57:30+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/blogs.bmj.com\/jmg\/files\/2021\/04\/Untitled-1.png\" \/>\n\t<meta property=\"og:image:width\" content=\"1920\" \/>\n\t<meta property=\"og:image:height\" content=\"1496\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"author\" content=\"hqqu\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@HuiQiQu\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"hqqu\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2021\\\/04\\\/27\\\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2021\\\/04\\\/27\\\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\\\/\"},\"author\":{\"name\":\"hqqu\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#\\\/schema\\\/person\\\/be0250f8d5b52412c3e7c222dabd591b\"},\"headline\":\"Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice (Contributed by Prof. Feng Zhang and Prof. Yanhua Wu)\",\"datePublished\":\"2021-04-27T00:23:14+00:00\",\"dateModified\":\"2026-02-23T22:57:30+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2021\\\/04\\\/27\\\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\\\/\"},\"wordCount\":134,\"commentCount\":0,\"publisher\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2021\\\/04\\\/27\\\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/files\\\/2021\\\/04\\\/Untitled-1-300x234.png\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2021\\\/04\\\/27\\\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2021\\\/04\\\/27\\\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\\\/\",\"url\":\"https:\\\/\\\/blogs.bmj.com\\\/jmg\\\/2021\\\/04\\\/27\\\/haploinsufficiency-in-non-homologous-end-joining-factor-1-induces-ovarian-dysfunction-in-humans-and-mice\\\/\",\"name\":\"Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice (Contributed by Prof. Feng Zhang and Prof. Yanhua Wu) - 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