Human HOX gene disorders.
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.
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. Electronic address: squinon@umich.edu.
Shane C
SC
Quinonez
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. Electronic address: innis@umich.edu.
Jeffrey W
JW
Innis
D000818:Animals; D000013:Congenital Abnormalities / Q000235:genetics*; D004195:Disease Models, Animal; D059472:Exome; D005801:Genes, Homeobox; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D051379:Mice; D008967:Molecular Biology; D005810:Multigene Family; D019683:Penetrance; D010641:Phenotype; D013577:Syndrome; D014714:Vertebrates / Q000235:genetics
Hand–foot–genital syndrome; Hox genes; Human Hox disorders; Synpolydactyly type II