Details

Autor(en) / Beteiligte

• Le Quesne Stabej, Polona
• Williams, Hywel J
• James, Chela
• Tekman, Mehmet
• Stanescu, Horia C
• Kleta, Robert
• Ocaka, Louise
• Lescai, Francesco
• Storr, Helen L
• Bitner-Glindzicz, Maria
• Bacchelli, Chiara
• Conway, Gerard S

Titel

STAG3 truncating variant as the cause of primary ovarian insufficiency

Ist Teil von

• European journal of human genetics : EJHG, 2016-01, Vol.24 (1), p.135-138

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.