Developmental gene diseases

Developmental genes are involved in various molecular mechanisms of cellular growth and differentiation. The identification of human dysmorphic syndromes have led to the detection of mutations in numerous of these developmental genes. A majority of them encode transcription factors. We focus this review on the description of developmental disorders due to mutation in transcription factors. These proteins bind DNA by specific structural domains and regulate the expression of target genes. HOX and PAX gene families involvement in human pathology is growing in complexity. Various mutations in different developmental genes add mental retardation to the phenotype, suggesting that these genes play a role in cranio-facial and central nervous system development. New gene families (SOX, SIX, TBX...) are emerging in developmental biology. Some transduction signal pathways - as the one mediated by Sonic Hedgehog - are well conserved during evolution and appear to be involved in normal human development, as shown by the phenotypical effects of mutations in genes that intervene at different stages of this signal transduction pathway.