Open AccessA homozygous truncating variant in GDF9 in siblings with primary ovarian insufficiency
Author(s) -
Kunal Verma,
Bryony A. Thompson,
James Wolfe,
Sarah Price,
Frida Djukiadmodjo,
Alison H. Trainer
Publication year - 2021
Publication title -
journal of assisted reproduction and genetics
Language(s) - English
Resource type - Journals
eISSN - 1573-7330
pISSN - 1058-0468
DOI - 10.1007/s10815-021-02144-x
Subject(s) - premature ovarian insufficiency , premature ovarian failure , growth differentiation factor 9 , biology , growth differentiation factor , genetics , mendelian inheritance , candidate gene , gene , endocrinology , medicine , bone morphogenetic protein , folliculogenesis , embryogenesis
Premature or primary ovarian insufficiency (POI) affects approximately 1% of women and can be due to a variety of causes. Genetic causes include syndromic and non-syndromic POI. There are several promising candidate genes for whom a clear Mendelian association with non-syndromic POI has not yet been conclusively established, including GDF9. GDF9 is an oocyte-secreted factor and is part of the TGF-beta superfamily of morphogens. It has an important role in follicular development and granulosa cell maturation. We report the case of two siblings with primary ovarian insufficiency (POI) and a homozygous truncating variant in GDF9 (c.604C>T; p.(Gln202*). This report helps establish a clear gene-disease association between GDF9 and POI and argues for routine evaluation for GDF9 variants in patients undergoing genomic investigation for POI.