GAPO syndrome: a new syndromic cause of premature ovarian insufficiency

Abstract

Premature ovarian insufficiency has the following causes: genetic, autoimmune, metabolic, infectious, and iatrogenic dysfunctions (including radiotherapy, chemotherapy and surgery). However, premature ovarian insufficiency remains without a definite cause in a substantial number of cases. This article describes GAPO syndrome in association with premature ovarian insufficiency, as well as a novel ANTXR1 gene mutation. Histopathological study of the ovaries of a woman with hypergonadotropic hypogonadism revealed extensive deposition of hyaline extracellular material, with bilateral parenchymal atrophy and follicular depletion. Molecular study revealed a novel ANTXR1 gene mutation. The homozygous c.378 + 3A > G transition at the consensus donor splice site of intron 4 was identified. Our results support the involvement of ANTRX1 gene mutations in deregulated extracellular matrix. In addition, our study identified a novel ANTXR1 mutation causing GAPO syndrome, indicating it as a new cause of early loss of ovarian function.

Keywords:

• GAPO syndrome
• premature ovarian insufficiency
• premature ovarian failure
• ANTXR1 gene
• extracellular matrix dysregulation

Conflict of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.

Source of funding

This study was partially funded by FAPESP (São Paulo Research Foundation), Brazil, grant # 2012/23669-0.