Limb malformations and the human HOX genes
Limb malformations and the human HOX genes
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DOI：
10.1002/ajmg.10776
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发表时间：
2002-10-15
期刊：
影响因子：
--
通讯作者：
Goodman, FR
中科院分区：
文献类型：
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作者：
Goodman, FR
HOX基因编码一个转录因子家族，在胚胎发育过程中对身体模式至关重要。和大多数脊椎动物一样，人类有39个HOX基因，它们被组织成4个簇，在中枢神经系统、轴骨骼、胃肠道和泌尿生殖道、外生殖器和四肢的发育中起主要作用。由人类HOX基因突变引起的前两种肢体畸形是合指畸形和手足生殖器综合征，分别由HOXD13和HOXA13突变引起。这篇综述描述了各种肢体畸形，现在已知是由这两个基因的特定不同突变引起的，包括多丙氨酸束扩张，无义突变和错义突变，许多具有表型后果，无法从以前的小鼠模型或HOX蛋白功能的知识中预测。肢体畸形也可能是由于涉及HOXD和HOXA基因簇的染色体缺失，以及影响单个或多个HOX基因的调控突变造成的。(C) 2002 Wiley-Liss, Inc。
HOX genes encode a family of transcription factors of fundamental importance for body patterning during embryonic development. Humans, like most vertebrates, have 39 HOX genes organized into four clusters, with major roles in the development of the central nervous system, axial skeleton, gastrointestinal and urogenital tracts, external genitalia, and limbs. The first two limb malformations shown to be caused by mutations in the human HOX genes were synpolydactyly and hand-foot-genital syndrome, which result from mutations in HOXD13 and HOXA13, respectively. This review describes a variety of limb malformations now known to be caused by specific different mutations in these two genes, including polyalanine tract expansions, nonsense mutations, and missense mutations, many with phenotypic consequences that could not have been predicted from previous knowledge of mouse models or HOX protein function. Limb malformations may also result from chromosomal deletions involving the HOXD and HOXA clusters, and from regulatory mutations affecting single or multiple HOX genes. (C) 2002 Wiley-Liss, Inc.