Genetic Factors and Orofacial Clefting.
Genetic Factors and Orofacial Clefting.
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DOI：
10.1053/j.sodo.2008.02.002
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发表时间：
2008-06-01
影响因子：
4.2
通讯作者：
Bullard, Steven A
中科院分区：
文献类型：
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作者：
Lidral, Andrew C;Moreno, Lina M;Bullard, Steven A
唇腭裂是最常见的面部先天缺陷，是由遗传和环境因素复杂的相互作用引起的。本综述的目的是以综合征型和非综合征型的唇腭裂为例，概述唇腭裂的遗传原因。虽然人类口面裂的基因鉴定过程还处于早期阶段，但步伐正在迅速加快。最近，已经确定了几个基因，它们在高达20%的所有裂缝中起联合作用。虽然这是向前迈出的重要一步，但很明显，其他导致裂缝的基因尚未被确定。正在进行的人类全基因组连锁研究已经确定了基因组中可能含有突变时导致口面裂的基因的区域，包括9号染色体上的一个主要基因，该基因在多个种族群体中呈阳性。目前，人们的努力集中在确定哪些基因在这些区域发生突变。此外，平行研究也在评估参与环境途径的基因。此外，统计遗传学家正在开发新的方法来表征基因-基因和基因-环境相互作用，以建立更好的模型，这种常见的出生缺陷的发病机制。这些研究的最终目标是为更准确的风险咨询和预防性治疗的发展提供知识。
Cleft lip with or without cleft palate is the most common facial birth defect and it is caused by a complex interaction between genetic and environmental factors. The purpose of this review is to provide an overview of the spectrum of the genetic causes for cleft lip and cleft palate using both syndromic and nonsyndromic forms of clefting as examples. Although the gene identification process for orofacial clefting in humans is in the early stages, the pace is rapidly accelerating. Recently, several genes have been identified that have a combined role in up to 20% of all clefts. While this is a significant step forward, it is apparent that additional cleft causing genes have yet to be identified. Ongoing human genome-wide linkage studies have identified regions in the genome that likely contain genes that when mutated cause orofacial clefting, including a major gene on chromosome 9 that is positive in multiple racial groups. Currently, efforts are focused to identify which genes are mutated in these regions. In addition, parallel studies are also evaluating genes involved in environmental pathways. Furthermore, statistical geneticists are developing new methods to characterize both gene-gene and gene-environment interactions to build better models for pathogenesis of this common birth defect. The ultimate goal of these studies is to provide knowledge for more accurate risk counseling and the development of preventive therapies.