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Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses.缩小差距:从综合征性到非综合征性颅缝早闭的遗传与基因组连续体
Curr Genet Med Rep. 2014 Sep 1;2(3):135-145. doi: 10.1007/s40142-014-0042-x.
2
Holoprosencephaly: signaling interactions between the brain and the face, the environment and the genes, and the phenotypic variability in animal models and humans.全前脑畸形:大脑与面部、环境与基因之间的信号相互作用,以及动物模型和人类中的表型变异性。
Wiley Interdiscip Rev Dev Biol. 2015 Jan-Feb;4(1):17-32. doi: 10.1002/wdev.161. Epub 2014 Oct 22.
3
Quantification of facial skeletal shape variation in fibroblast growth factor receptor-related craniosynostosis syndromes.成纤维细胞生长因子受体相关颅缝早闭综合征中面部骨骼形状变异的量化
Birth Defects Res A Clin Mol Teratol. 2014 Apr;100(4):250-9. doi: 10.1002/bdra.23228. Epub 2014 Feb 27.
4
Embryonic bauplans and the developmental origins of facial diversity and constraint.胚胎模式与面部多样性和约束的发育起源。
Development. 2014 Mar;141(5):1059-63. doi: 10.1242/dev.099994.
5
Perspectives and challenges in advancing research into craniofacial anomalies.颅面畸形研究进展的观点和挑战。
Am J Med Genet C Semin Med Genet. 2013 Nov;163C(4):213-7. doi: 10.1002/ajmg.c.31383. Epub 2013 Oct 18.
6
Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.颅缝早闭的基因型与临床护理相关性:来自澳大利亚和新西兰 630 例患者队列的研究结果。
Am J Med Genet C Semin Med Genet. 2013 Nov;163C(4):259-70. doi: 10.1002/ajmg.c.31378. Epub 2013 Oct 11.
7
Facial dysostoses: Etiology, pathogenesis and management.面骨发育不全:病因、发病机制与治疗。
Am J Med Genet C Semin Med Genet. 2013 Nov;163C(4):283-94. doi: 10.1002/ajmg.c.31375. Epub 2013 Oct 4.
8
Stakeholders in outcome measures: review from a clinical perspective.结局指标的利益相关者:从临床角度的综述。
Clin Orthop Relat Res. 2013 Nov;471(11):3426-36. doi: 10.1007/s11999-013-3265-3.
9
Hypothesis-generating research and predictive medicine.生成假说的研究与预测医学。
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10
A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9.一项全基因组关联研究鉴定出非综合征性矢状缝早闭的易感基因座,位于 BMP2 附近和 BBS9 内。
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直面颅面研究进展中的挑战。

Facing up to the challenges of advancing Craniofacial Research.

作者信息

Trainor Paul A, Richtsmeier Joan T

机构信息

Stowers Institute for Medical Research, Kansas City, Missouri.

Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas.

出版信息

Am J Med Genet A. 2015 Jul;167(7):1451-4. doi: 10.1002/ajmg.a.37065. Epub 2015 Mar 28.

DOI:10.1002/ajmg.a.37065
PMID:25820983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4478228/
Abstract

Craniofacial anomalies are among the most common human birth defects and have considerable functional, aesthetic, and social consequences. The early developmental origin as well as the anatomical complexity of the head and face render these tissues prone to genetic and environmental insult. The establishment of craniofacial clinics offering comprehensive care for craniofacial patients at a single site together with international research networks focused on the origins and treatment of craniofacial disorders has led to tremendous advances in our understanding of the etiology and pathogenesis of congenital craniofacial anomalies. However, the genetic, environmental, and developmental sources of many craniofacial disorders remain unknown. To overcome this problem and further advance craniofacial research, we must recognize current challenges in the field and establish priority areas for study. We still need (i) a deeper understanding of variation during normal development and within the context of any disorder, (ii) improved genotyping and phenotyping and understanding of the impact of epigenetics, (iii) continued development of animal models and functional analyses of genes and variants, and (iv) integration of patient derived cells and tissues together with 3D printing and quantitative assessment of surgical outcomes for improved practice. Only with fundamental advances in each of these areas will we be able to meet the challenge of translating potential therapeutic and preventative approaches into clinical solutions and reduce the financial and emotional burden of craniofacial anomalies.

摘要

颅面畸形是最常见的人类出生缺陷之一,会产生相当大的功能、美学和社会影响。头部和面部的早期发育起源以及解剖学复杂性使这些组织容易受到遗传和环境损伤。颅面诊所的建立为颅面患者在单一地点提供全面护理,同时国际研究网络专注于颅面疾病的起源和治疗,这使得我们对先天性颅面畸形的病因和发病机制的理解有了巨大进展。然而,许多颅面疾病的遗传、环境和发育根源仍然未知。为了克服这一问题并进一步推进颅面研究,我们必须认识到该领域当前的挑战,并确定优先研究领域。我们仍然需要:(i)更深入地了解正常发育过程中的变异以及在任何疾病背景下的变异;(ii)改进基因分型和表型分析,并了解表观遗传学的影响;(iii)持续开发动物模型以及对基因和变异进行功能分析;(iv)整合患者来源的细胞和组织,以及3D打印和手术结果的定量评估,以改善临床实践。只有在这些领域都取得根本性进展,我们才能应对将潜在治疗和预防方法转化为临床解决方案的挑战,并减轻颅面畸形带来的经济和情感负担。