Characterisation of molecular defects in X-linked amelogenesis imperfecta (AIH1).

Amelogenins are an heterogenous family of proteins produced by ameloblasts of the enamel organ during tooth development.
Disturbances of enamel formation occur in amelogenesis imperfecta, a clinically heterogenous group of inherited disorders characterised by defective enamel biomineralisation.
An amelogenin gene, AMGX, has been mapped to the short of the X chromosome (Xp22. 1-p22. 3) and has been implicated in the molecular pathology of X-linked amelogenesis imperfecta (AIH1). We have identified three families exhibiting AIH1 and screened the AMGX gene for mutations using single-strand conformational polymorphism analysis and DNA sequencing.
Three novel mutations were identified  a C-T substitution in exon 5, and a G-T substitution and single cytosine deletion in exon 6, confirming the existence of extensive allelic heterogeneity in this condition.
The identification of family-specific mutations will enable early identification of affected individuals and correlation of clinical phenotype with genotype will facilitate an objective system of disease classification.

