title: 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.
authors.affiliation: a Department of Gynecology and Obstetrics, School of Medical Sciences , University of Campinas , Campinas , SP , Brazil.
authors.forename: C L
authors.initials: CL
authors.lastname: Benetti-Pinto
authors.affiliation: b School of Medical Sciences , University of Campinas , Campinas , SP , Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Ferreira
authors.affiliation: c Department of Pathology, School of Medical Sciences , University of Campinas , Campinas , SP , Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Andrade
authors.affiliation: a Department of Gynecology and Obstetrics, School of Medical Sciences , University of Campinas , Campinas , SP , Brazil.
authors.forename: D A
authors.initials: DA
authors.lastname: Yela
authors.affiliation: d Center of Molecular Biology and Genetic Engineering , University of Campinas , Campinas , SP , Brazil.
authors.forename: M P
authors.initials: MP
authors.lastname: De Mello
mesh_terms: D000328:Adult; D000505:Alopecia / Q000150:complications* / Q000235:genetics; D000848:Anodontia / Q000150:complications* / Q000235:genetics; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006130:Growth Disorders / Q000150:complications* / Q000235:genetics; D006720:Homozygote; D006801:Humans; D006818:Hyalin; D007006:Hypogonadism / Q000235:genetics; D008840:Microfilament Proteins; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D015418:Optic Atrophies, Hereditary / Q000150:complications* / Q000235:genetics; D010053:Ovary / Q000473:pathology; D016649:Primary Ovarian Insufficiency / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics
chemical_list: C473287:ANTXR1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface
keywords: ANTXR1 gene; GAPO syndrome; extracellular matrix dysregulation; premature ovarian failure; premature ovarian insufficiency