Genetics of limb anomalies in humans

Abstract

The limbs have an essential function in all vertebrates. In animals, the key genes that are involved in the growth and patterning of the limb buds, and of the development of the complex extremities, have been identified and their interactions recognized. Aided by these discoveries, human genetics has also been able to identify, or at least localize, certain genes responsible for anomalies of the limbs. These malformations are isolated or associated with anomalies of other developmental fields, according to the expression domain of the gene involved. Increasing knowledge of the embryology and genes involved has lead to a regrouping of malformation manifestations in genetics terms. Clear genotype-phenotype correlations are difficult to establish owing to the interlinking network of genetic signals underlying limb development.