GAPO syndrome: a new syndromic cause of premature ovarian insufficiency

Benetti‐Pinto, Cristina Laguna; Ferreira, Valeska; Andrade, Liliana Aparecida Lucci De Angelo; Yela, Daniela Angerame; Mello, Maricilda Palandi de

doi:10.1080/13697137.2016.1200551

Cited by 14 publications

(9 citation statements)

References 15 publications

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“…GAPO syndrome, another form of premature aging and premature follicle depletion, is caused by mutations of the anthrax toxin receptor 1 gene ANTXR1 [74]. The protein has been involved in cell attachment and migration.…”

Section: Premature Aging Syndromesmentioning

confidence: 99%

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Huhtaniemi

Hovatta

Marca

et al. 2018

Trends in Endocrinology & Metabolism

157

137

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Primary ovarian insufficiency (POI) affects ∼1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of >60 genes emphasize high genetic heterogeneity. Genome-wide association studies have revealed a shared genetic background between POI and reproductive aging. NGS will provide a genetic diagnosis leading to genetic/therapeutic counseling: first, defects in meiosis or DNA repair genes may predispose to tumors; and second, specific gene defects may predict the risk of rapid loss of a persistent ovarian reserve, an important determinant in fertility preservation. Indeed, a recent innovative treatment of POI by in vitro activation of dormant follicles proved to be successful.

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Section: Premature Aging Syndromesmentioning

confidence: 99%

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Huhtaniemi

Hovatta

Marca

et al. 2018

Trends in Endocrinology & Metabolism

157

137

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“…Arg99_Arg126del was indicated to result in exon 4 skipping in a Brazilian GAPO syndrome patient also affected with premature ovarian insufficiency (Benetti-Pinto et al, 2016).…”

Section: Discussionmentioning

confidence: 98%

“…To date, nine different biallelic ANTXR1 variants have been suggested as etiologic for GAPO syndrome [Bayram et al 2014; Benetti-Pinto et al 2016; Chattopadhyay et al 2017; Salas-Alanis et al 2016; Stranecky et al 2013] (Fig. 2c).…”

Section: Discussionmentioning

confidence: 99%

“…Two missense variants (c.410A>T [p.Gln137Leu] and c.265G>A [p.Gly89Arg]) located in the VWA domain were also identified in two families affected with GAPO syndrome, one of Hispanic and one of South Asian descent, respectively [Chattopadhyayet al 2017; Salas-Alaniset al 2016]. In addition, a splice site mutation c.378+3A>G (p.[Arg99_Arg126del]) was indicated to result in exon 4 skipping in a Brazilian GAPO syndrome patient also affected with premature ovarian insufficiency [Benetti-Pinto et al 2016]. …”

Section: Discussionmentioning

confidence: 99%

“…To date, nine different biallelic ANTXR1 variants have been suggested as etiologic for GAPO syndrome (Bayram et al, 2014;Benetti-Pinto, Ferreira, Andrade, Yela, & De Mello, 2016;Chattopadhyay et al, 2017;Salas-Alanis et al, 2016;Stranecky et al, 2013) (Figure 2c | 1019 syndrome patients (Stranecky et al, 2013). The nonsense variants reside within the VWA domain, whereas the splice site variant was predicted to abolish a splicing acceptor site of the ANTXR1 transcript.…”

Section: Discussionmentioning

confidence: 99%

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A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis

Dinçkan¹,

Du²,

Akdemir³

et al. 2018

American J of Med Genetics Pt A

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Tooth development is regulated by multiple genetic pathways, which ultimately drive the complex interactions between the oral epithelium and mesenchyme. Disruptions at any time point during this process may lead to failure of tooth development, also known as tooth agenesis (TA). TA is a common craniofacial abnormality in humans and represents the failure to develop one or more permanent teeth. Many genes and potentially subtle variants in these genes contribute to the TA phenotype. We report the clinical and genetic impact of a rare homozygous ANTXR1 variant (c.1312C>T), identified by whole exome sequencing (WES), in a consanguineous Turkish family with TA. Mutations in ANTXR1 have been associated with GAPO (growth retardation, alopecia, pseudoanodontia, and optic atrophy) syndrome and infantile hemangioma, however no clinical characteristics associated with these conditions were observed in our study family. We detected the expression of Antxr1 in oral and dental tissues of developing mouse embryos, further supporting a role for this gene in tooth development. Our findings implicate ANTXR1 as a candidate gene for isolated TA, suggest the involvement of specific hypomorphic alleles, and expand the previously known ANTXR1-associated phenotypes.

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GAPO syndrome in seven new patients: Identification of five novel ANTXR1 mutations including the first large intragenic deletion

Abdel‐Hamid

Ismail

Zaki

et al. 2018

American J of Med Genetics Pt A

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GAPO syndrome is a very rare disorder characterized by growth retardation, alopecia, pseudoanodontia and progressive optic atrophy. It is caused by biallelic mutations in the ANTXR1 gene. Herein, we describe the clinical and molecular findings of seven new patients with GAPO syndrome. Our patients presented with the characteristic clinical features of the syndrome except for one patient who did not display total alopecia till the age of two years. Strikingly, optic atrophy and glaucoma were observed in all patients and one patient showed keratopathy in addition. Moreover, craniosynstosis was an unusual associated finding in one patient. Mutational analysis of ANTXR1 gene identified five novel homozygous mutations including two frameshift, two splice site and a large intragenic deletion of exon 3. Our results reinforce the clinical characteristics of the syndrome, expand the mutational spectrum and provide more insights into the role of the ANTXR1 protein in the regulation of extracellular matrix.

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GAPO syndrome: a new syndromic cause of premature ovarian insufficiency

Cited by 14 publications

References 15 publications

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis

GAPO syndrome in seven new patients: Identification of five novel ANTXR1 mutations including the first large intragenic deletion

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