An Axin2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a Chinese female monochorionic diamniotic twin family,Hereditas

当前位置： X-MOL 学术 › Hereditas › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

An Axin2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a Chinese female monochorionic diamniotic twin family
Hereditas ( IF 2.1 ) Pub Date : 2021-06-16 , DOI: 10.1186/s41065-021-00182-0
Jin Xu _{1,

2,

3} , Qing Yan ₄ , Chengcheng Song ₅ , Jingjia Liang _{1,

2} , Liang Zhao ₆ , Xin Zhang _{1,

2} , Zhenkun Weng _{1,

2} , Cheng Xu _{1,

2} , Qian Liu _{1,

2} , Shuqin Xu _{1,

2} , Lu Pang _{1,

2} , Liye Zhang _{1,

2} , Yuan Sun ₂ , Gang Wang ₄ , Aihua Gu _{1,

2}

Affiliation

Craniosynostosis, defined as premature fusion of one or more cranial sutures, affects approximately 1 in every 2000–2500 live births. Sagittal craniosynostosis (CS), the most prevalent form of isolated craniosynostosis, is caused by interplay between genetic and perinatal environmental insults. However, the underlying details remain largely unknown. The proband (a female monochorionic twin diagnosed with CS), her healthy co-twin sister and parents were enrolled. Obstetric history was extracted from medical records. Genetic screening was performed by whole exome sequencing (WES) and confirmed by Sanger sequencing. Functional annotation, conservation and structural analysis were predicted in public database. Phenotype data of Axin2 knockout mice was downloaded from The International Mouse Phenotyping Consortium (IMPC, http://www.mousephenotype.org ). Obstetric medical records showed that, except for the shared perinatal risk factors by the twins, the proband suffered additional persistent breech presentation and intrauterine growth restriction. We identified a heterozygous mutation of Axin2 (c.1181G > A, p.R394H, rs200899695) in monochorionic twins and their father, but not in the mother. This mutation is not reported in Asian population and results in replacement of Arg at residue 394 by His (p.R394H). Arg 394 is located at the GSK3β binding domain of Axin2 protein, which is highly conserved across species. The mutation was predicted to be potentially deleterious by in silico analysis. Incomplete penetrance of Axin2 haploinsufficiency was found in female mice. Axin2 (c.1181G > A, p.R394H, rs200899695) mutation confers susceptibility and perinatal risk factors trigger the occurrence of sagittal craniosynostosis. Our findings provide a new evidence for the gene-environment interplay in understanding pathogenesis of craniosynostosis in Chinese population.

更新日期：2021-06-17

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11