Gene/environment interactions in craniosynostosis: A brief review

Durham, Emily L.; Howie, R. Nicole; Cray, James J.

doi:10.1111/ocr.12153

Cited by 25 publications

(32 citation statements)

References 36 publications

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“…1). However, none of candidate germline or somatic mutations were proband-speci c. As geneenvironment interactions have been revealed in the pathogenesis of craniosynostosis [5,15], we wonder whether the adverse intrauterine exposures (environment) triggered the susceptible individual (II-1) to develop sagittal craniosynostosis. Based on this hypothesis, we re-analyzed our sequencing data and identi ed a heterozygous missense mutation of AXIN2 (c.1181G>A, p.R394H) in the leukocytes of subjects I-1, II-1 and II-2, and skull periosteum tissue of subject II-1.…”

Section: Mutation Analysismentioning

confidence: 99%

“…The pathoetiology of NCS, involving interplay between genetic and environmental factors, is still not well de ned [5][6][7][8]. FGF ( broblast growth factor), BMP (bone morphogenic protein), Wnt (wingless-type integration sites) pathways are the major regulators in suture biology [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…Non-genetic risk factors, such as intrauterine constraint, twin gestation, low birth weight, malnutrition, premature delivery, maternal thyroid disorders, gestational diabetes, virus infectious, can either cause or exacerbate craniosynostosis [7,[11][12][13][14]. Although several ndings demonstrate the interactions between genetic and environmental in uences that contribute to prematurely fused sutures [5,15], more evidence are still needed to delineate the institutional patterns. Monochorionic (MC) twins, sharing almost the same genome, offer a unique opportunity to study the gene/environment interactions, for the healthy twin as an ideal control.…”

Section: Introductionmentioning

confidence: 99%

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A novel AXIN2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a monochorionic diamniotic twin family

Xu¹,

Yan²,

Song³

et al. 2020

Preprint

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Background: Craniosynostosis, the premature fusion of one or more cranial sutures, affects approximately 1 in every 2000-2500 live births. The etiology of sagittal craniosynostosis, the most prevalent form of isolated craniosynostosis, involves interplay between genetic and environmental insults, such as perinatal risk factors. However, the detailed information still remains largely unknown. Methods: The proband, a female monochorionic twin diagnosed with sagittal craniosynostosis, as well as her healthy twin sister and parents, were enrolled in our study. The obstetric medical records were retrospectively reviewed. Genetic cause was investigated by whole exome sequencing (WES) and further confirmed by Sanger sequencing.Results: We identified a novel heterozygous mutation of AXIN2 (c.1181G>A) in monochorionic twins and their father. However, only the proband presented sagittal craniosynostosis. This mutation results in the replacement of Arg at residue 394 by His (p.R394H). Arg 394 is located at the GSK3β binding domain of the AXIN2 protein, which is highly conserved across species. The obstetric medical records revealed that the proband had additional persistent breech presentation and intrauterine growth restriction, except for the perinatal risk factors shared by the twins.Conclusions: Based on the role of AXIN2 in craniosynostosis development and deleterious prediction in silico of AXIN2 (c.1181G>A: p.R394H), we speculate that this particular mutation confers susceptibility to sagittal craniosynostosis, while extra environmental insults are also involved in the pathogenesis of this case. Our findings provide a new evidence for the gene-environment interplay in understanding pathogenesis of craniosynostosis.

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Section: Mutation Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel AXIN2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a monochorionic diamniotic twin family

Xu¹,

Yan²,

Song³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Even though treatments for birth defects have improved, they continue to be a major public health concern. This is due to the fact that the etiology of most birth defects remains unknown (Durham, Howie, & Cray, 2017;Harris et al, 2017;Khokha, Mitchell, & Wallingford, 2017). Thus, to develop strategies that either prevent or treat birth defects, we need to identify their underlying causes.…”

Section: Birth Defects Have Complex Etiologiesmentioning

confidence: 99%

Animal models of gene–alcohol interactions

Lovely

2019

Birth Defects Research

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Most birth defects arise from complex interactions between multiple genetic and environmental factors. However, our current understanding of how these interactions and their contributions affect birth defects remains incomplete. Human studies are limited in their ability to identify the fundamental causes of birth defects due to ethical and practical limitations. Animal models provide a great number of resources not available to human studies and they have been critical in advancing our understanding of birth defects and the complex interactions that underlie them. In this review, we discuss the use of animal models in the context of gene–environment interactions that underlie birth defects. We focus on alcohol which is the most common environmental factor associated with birth defects. Prenatal alcohol exposure leads to a wide range of cognitive impairments and structural deficits broadly termed fetal alcohol spectrum disorders (FASD). We discuss the broad impact of prenatal alcohol exposure on the developing embryo and elaborate on the current state of gene–alcohol interactions. Additionally, we discuss how animal models have informed our understanding of the genetics of FASD. Ultimately, these topics will provide insight into the use of animal models in understanding gene–environment interactions and their subsequent impact on birth defects.

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“…Through genetic studies, tens of genes are shown to be associated with craniosynostosis (Twigg and Wilie, 2015), providing a foundation for further elucidation of the mechanism of the trait. Like any phenotypes, there should also be environmental contributions to craniosynostosis (Shashi and Hart, 2002; Zeiger et al, 2002; Durham et al, 2017), illustrated by an observation of identical twins with discordant craniosynostosis (Magge et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

A Higher Proportion of Craniosynostosis Genes Are Cancer Driver Genes

Misra

Shih

Yan

et al. 2019

Preprint

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Craniosynostosis (CRS) is a congenital abnormality deformity with a heterogenous genetic contribution. Previously, there are two attempts to collect genes that are genetically associated with craniosynostosis and some related syndromes with 57 (Twigg and Wilkie, 2015) and 39 (Goos and Mathijssen, 2019) genes identified, respectively. We expanded this list of craniosynostosis genes by adding another 17 genes with an updated literature search. These genes are shown to be more likely to be intolerant to functional mutations. Of these 113 craniosynostosis genes, 21 (19% vs. 1.5% baseline frequency) are cancer driver genes, a 14-fold enrichment. The cancer-craniosynostosis connection is further validated by an over-representation analysis of craniosynostosis genes in KEGG cancer pathway and several cancer related gene-sets. Many cancer-craniosynostosis overlapping genes participate in intracellular signaling pathways, which play a role in both development and cancer. This connection can be viewed from the oncogenesis recapitulates ontogenesis framework. Nineteen craniosynostosis genes are transcription factor genes (16.8% vs. 8.2% baseline), and craniosynostosis genes are also enriched in targets of certain transcription factors or micro RNAs.

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Gene/environment interactions in craniosynostosis: A brief review

Cited by 25 publications

References 36 publications

A novel AXIN2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a monochorionic diamniotic twin family

A novel AXIN2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a monochorionic diamniotic twin family

Animal models of gene–alcohol interactions

A Higher Proportion of Craniosynostosis Genes Are Cancer Driver Genes

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