Molecular analysis of non-syndromic preaxial polydactyly: preaxial polydactyly type-IV and preaxial polydactyly type-I.

Human GLI3 gene mutations have been identified in several phenotypes of digital abnormality such as Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type-IV (PPD-IV) and postaxial polydactyly. However, the different phenotypes resulting from GLI3 mutations have not yet been properly defined. We have experienced two types of digital abnormality without other complicating developmental defects; a family with foot PPD-IV with syndactyly of the third and fourth fingers, and four sporadic cases with biphalangeal thumb polydactyly (PPD-I). The genes responsible for syndactyly of the third and fourth fingers (syndactyly type-I) and PPD-I have not yet been identified; we therefore examined the involvement of the GLI3 gene in these subtypes of digital abnormality. We found a non-sense mutation in the GLI3 gene in the family with foot PPD-IV accompanied with hand syndactyly of the third and fourth fingers, but no mutations were detected in the GLI3 gene in the four other cases with PPD-I alone. Thus, the phenotype of foot PPD-IV accompanied with hand syndactyly of the third and fourth fingers may result from a GLI3 mutation, whereas the PPD-I phenotype alone is not caused by GLI3 gene defect. These results will help to define the phenotypic spectrum of GLI3 morphopathies, which have been recently proposed.