Quinonez Shane C, Innis Jeffrey W
University of Michigan, Department of Pediatrics, Division of Pediatric Genetics, 1500 East Medical Center Drive, D5240 MPB/Box 5718, Ann Arbor, MI 48109-5718, USA.
University of Michigan, Department of Pediatrics, Division of Pediatric Genetics, 1500 East Medical Center Drive, D5240 MPB/Box 5718, Ann Arbor, MI 48109-5718, USA; University of Michigan, Department of Human Genetics, 1241 E. Catherine, 4909 Buhl Building, Ann Arbor, MI 48109-5618, USA.
Mol Genet Metab. 2014 Jan;111(1):4-15. doi: 10.1016/j.ymgme.2013.10.012. Epub 2013 Oct 29.
The Hox genes are an evolutionarily conserved family of genes, which encode a class of important transcription factors that function in numerous developmental processes. Following their initial discovery, a substantial amount of information has been gained regarding the roles Hox genes play in various physiologic and pathologic processes. These processes range from a central role in anterior-posterior patterning of the developing embryo to roles in oncogenesis that are yet to be fully elucidated. In vertebrates there are a total of 39 Hox genes divided into 4 separate clusters. Of these, mutations in 10 Hox genes have been found to cause human disorders with significant variation in their inheritance patterns, penetrance, expressivity and mechanism of pathogenesis. This review aims to describe the various phenotypes caused by germline mutation in these 10 Hox genes that cause a human phenotype, with specific emphasis paid to the genotypic and phenotypic differences between allelic disorders. As clinical whole exome and genome sequencing is increasingly utilized in the future, we predict that additional Hox gene mutations will likely be identified to cause distinct human phenotypes. As the known human phenotypes closely resemble gene-specific murine models, we also review the homozygous loss-of-function mouse phenotypes for the 29 Hox genes without a known human disease. This review will aid clinicians in identifying and caring for patients affected with a known Hox gene disorder and help recognize the potential for novel mutations in patients with phenotypes informed by mouse knockout studies.
Hox基因是一个在进化上保守的基因家族，它们编码一类重要的转录因子，在众多发育过程中发挥作用。自最初发现以来，人们已经获得了大量关于Hox基因在各种生理和病理过程中所起作用的信息。这些过程涵盖了从在发育胚胎的前后模式形成中起核心作用到在肿瘤发生中的作用（尚未完全阐明）。在脊椎动物中，共有39个Hox基因，分为4个独立的簇。其中，已发现10个Hox基因的突变会导致人类疾病，其遗传模式、外显率、表现度和发病机制存在显著差异。本综述旨在描述这10个导致人类表型的Hox基因种系突变所引起的各种表型，特别强调等位基因疾病之间的基因型和表型差异。随着未来临床全外显子组和基因组测序的日益应用，我们预测可能会鉴定出更多导致不同人类表型的Hox基因突变。由于已知的人类表型与特定基因的小鼠模型非常相似，我们还综述了29个尚无已知人类疾病的Hox基因的纯合功能丧失小鼠表型。本综述将帮助临床医生识别和护理受已知Hox基因疾病影响的患者，并有助于认识到在具有由小鼠基因敲除研究提供信息的表型的患者中出现新突变的可能性。
