STAG3 truncating variant as the cause of primary ovarian insufficiency

Le Quesne Stabej, P., Williams, H.J. ORCID: https://orcid.org/0000-0001-7758-0312, James, C., Tekman, M., Stanescu, H.C., Kleta, R., Ocaka, L., Lescai, F., Storr, H.L., Bitner-Glindzicz, M., Bacchelli, C., Conway, G.S. and Sgene, G.O. 2016. STAG3 truncating variant as the cause of primary ovarian insufficiency. European Journal of Human Genetics 24 (1) , pp. 135-138. 10.1038/ejhg.2015.107

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Abstract

Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI is heterogeneous with only a few causative genes having been discovered so far. Our objective was to determine the genetic cause of POI in a consanguineous Lebanese family with two affected sisters presenting with primary amenorrhoea and an absence of any pubertal development. Multipoint parametric linkage analysis was performed. Whole-exome sequencing was done on the proband. Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family. Exome sequencing combined with linkage analyses offers a powerful tool to efficiently find novel genetic causes of rare, heterogeneous disorders, even in small single families. This is only the second report of a STAG3 variant; the first STAG3 variant was recently described in a phenotypically similar family with extreme POI. Identification of an additional family highlights the importance of STAG3 in POI pathogenesis and suggests it should be evaluated in families affected with POI.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Nature Publishing Group
ISSN:	1018-4813
Date of First Compliant Deposit:	30 January 2020
Date of Acceptance:	3 April 2015
Last Modified:	05 May 2023 21:29
URI:	https://orca.cardiff.ac.uk/id/eprint/128297

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