Solving the Puzzle of Pathogenic Mutations in Premature Ovarian Insufficiency

Solving the Puzzle of Pathogenic Mutations in Premature Ovarian Insufficiency

Table of Contents

What is Premature Ovarian Insufficiency?

Premature ovarian insufficiency, also called POI, is a common cause of female infertility, affecting 3.7% of women before the age of 40. It occurs when the ovaries stop functioning prematurely, though the causes underlying this cessation of function are highly heterogeneous. Current research suggests that contributing factors could include spontaneous genetic mutations, autoimmune diseases, severe infections, and more.

Several lines of evidence suggest that a large proportion of cases may be precipitated by a genetic basis for the disease. Uncovering the genes underlying the pathogenesis of POI could be extremely useful for diagnostic purposes and to identify new therapeutic targets for further research.

Uncovering the Pathogenic Mutations Behind POI

High-throughput sequencing analyses have so far identified approximately 90 genes linked to either isolated or syndromic POI, but these known variants account for a small fraction of POI patients due to the high genetic heterogeneity of the disease. In a recent Nature Medicine paper, Ke et. al. perform one of, if not the largest, whole exome sequencing analyses of POI patients to date.

From a cohort of 1,030 patients, the authors detected 195 pathogenic or likely pathogenic variants in 59 genes previously implicated as contributors to POI. After comparison to a control cohort of 5,000 patients without POI, the authors identified 20 novel genes associated with POI. Their functions were clearly entwined with key reproductive biological processes, including gonadogenesis, meiosis, folliculogenesis, and ovulation.

However, even with these novel genes in combination with known POI-related genes, these variants only accounted for causes of 23.5% of the patient cases. This study illustrates the unique challenge posed by highly heterogeneous diseases like POI, where careful combinations of studies of external and genetic factors will be needed to diagnose a given patient’s exact cause and inform their treatment options.

By understanding the need for a multi-disciplinary approach to diagnosis, healthcare providers can ensure that patients receive the most effective and personalized treatment plan based on their specific cause of POI. Additionally, this information can also inform future research studies aimed at improving the understanding and management of POI.

Outsourcing Bioinformatics Analysis: How Bridge Informatics Can Help

Many of our clients at Bridge Informatics are pursuing these kinds of research questions with sophisticated bioinformatics approaches like whole-exome sequencing analysis. From pipeline development and software engineering to deploying existing bioinformatics tools, Bridge Informatics can help you on every step of your research journey. 
As experts across data types from cutting-edge sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing, and interpreting genomic and transcriptomic data. Bridge Informatics’ bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis. Click here to schedule a free introductory call with a member of our team.

Jane Cook, Biochemist & Content Writer, Bridge Informatics

Jane Cook, the leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas. While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email [email protected] or [email protected].

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