Boyadjiev S A, Jabs E W
Department of Pediatrics, McKusick-Nathans Institute of Genetic Medicine, Center for Craniofacial Development and Disorders, The Johns Hopkins University, Baltimore, MA 21287-3914, USA.
Clin Genet. 2000 Apr;57(4):253-66. doi: 10.1034/j.1399-0004.2000.570403.x.
In this review, we summarize the current genetic information on human developmental disorders found in Online Mendelian Inheritance in Man (OMIM). The OMIM catalogues human phenotypes and genotypes and relevant mouse models. Among the more than 11005 genetic disorders and loci, we found at least 1231 human conditions with known gene mutationsffWe searched for human developmental disorders that present with structural defects during the perinatal period, and identified 162 such entries. We classified these entries by phenotypic features (e.g., skeletal dysplasias, axis and laterality defects, or eye disorders) and by the type of gene mutated (e.g., genes coding for transcription factors, structural proteins, enzymes, or receptors). Thirty-eight entries have allelic variants with gene mutations causing different functional consequences, thereby altering their interactions with modifying genes. Thirty-two entries show genetic heterogeneity due to either functional redundancy of more than one gene or genes that interact in common developmental pathways. Although many different types of genes are mutated in developmental disorders, we found that the disease genes are transcription factors in 49 entries. Mouse models are available for many of the human conditions, with the majority of these mutants being secondary to null mutations. These data allow us to begin to elucidate the complex developmental pathways involved in the molecular pathogenesis of human malformations.
在本综述中，我们总结了在线人类孟德尔遗传（OMIM）中发现的关于人类发育障碍的当前遗传信息。OMIM编目了人类表型、基因型及相关小鼠模型。在超过11005种遗传疾病和基因座中，我们发现至少1231种人类疾病存在已知基因突变。我们搜索了在围产期出现结构缺陷的人类发育障碍，并识别出162个此类条目。我们根据表型特征（如骨骼发育异常、轴和侧向缺陷或眼部疾病）以及突变基因的类型（如编码转录因子、结构蛋白、酶或受体的基因）对这些条目进行分类。38个条目具有等位基因变体，其基因突变会导致不同的功能后果，从而改变它们与修饰基因的相互作用。32个条目表现出遗传异质性，原因要么是多个基因的功能冗余，要么是在共同发育途径中相互作用的基因。尽管在发育障碍中有许多不同类型的基因发生突变，但我们发现有49个条目的致病基因是转录因子。许多人类疾病都有对应的小鼠模型，其中大多数突变体是由无效突变导致的。这些数据使我们能够开始阐明人类畸形分子发病机制中涉及的复杂发育途径。
