An Amelogenin Gene Mutation Associated with X-linked Amelogenesis Imperfecta

Abstract

A kindred was described with X-linked hypo-maturation Amelogenesis Imperfecta, in which the teeth of the propositus had mottled yellowish white enamel and his mother had vertical bands of opaque white and translucent enamel (Sauk et al., Am. J. Hum. Genet., 24, 267, 1972). Members of this family were contacted to obtain blood samples, in order to search for a mutation within the coding region of the X-chromosomal amelogenin gene. Primers were designed to amplify by the polymerase chain reaction (PCR) the coding regions: PCR products were sequenced directly, or cloned and sequenced. A point mutation was identified in the sequence encoding the 8th amino acid (pro > thr) of exon-6 of three affected family members. Two unaffected sisters of the propositus each had the normal DNA sequence as described by Salido et al. (Am. J. Hum. Genet., 50, 303, 1992). This proline is conserved in human X and Y chromosomal amelogenin genes, as well as in cow, pig, mouse, rat and opossum amelogenins, and is located within a highly conserved region of the protein. This mutation is significant in that it localizes a domain in the amelogenin protein predicted to be required for normal enamel formation. This study was supported by NIH grants DE10149 (CWG) and DE08239 (JR).