Enamel ultrastructure an protein content in X-linked amelogenesis imperfecta J. Tim Wright, DDS, MSa Michael J. Aldred, BDS, PhD, FDSRCS, MRCPathb Peter J.M. Crawford, BDS, MScD, FDSRCSC Jenifer Kirkham, PhD,d and Colin Robinson, PhD,e Chapel Hill, N.C., Queensland, Australia, Bristol, England, and Leeds, England UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL, UNIVERSITY OF QUEENSLAND, UNIVERSITY OF BRISTOL, UNIVERSITY OF LEEDS, AND LEEDS DENTAL INSTITUTE X-linked amelogenesis imperfecta has been proven in a number of families to be !inked to or involve a variety of mutations in the X chromosome amelogenin gene. The purpose of this study was to characterize the enamel ultrastructure and enamel protein in a kindred affected by X-!inked amelogenesis imperfecta. Exfoliated primary teeth were obtained from two related persons (one male, one female) who had X-linked amelogenesis imperfecta with marked hypoplasia. Normal enamel (age and sex matched) was used as the control for all analyses. The teeth were evaluated using light microscopy, scanning electron microscopy, and microradiography. The enamel of the heterozygous female was hypoplastic and rough with marked surface depressions. Enamel beneath these depressions was poorly organized and lacked a prismatic structure. The affected male had very thin enamel (-40 pm) that also lacked an organized structure. Enamel protein from the teeth of the heterozygous female and the control was characterized using amino acid analysis. The protein content of the enamel of the female with amelogenesis imperfecta was 0.40% (N = 1) whereas the control enamel ranged from 0.17% to 0.45% (N = 4; mean = 0.34%). This study indicates that although the enamel in both the male and female with X-linked amelogenesis imperfecta displayed marked structural abnormalities the enamel protein was similar in quantity and amino acid composition for normal and X-linked amelogenesis imperfecta (female) enamel. The amelogenesis imperfecta gene defect in this family, although causing dramatic structural changes, appears not to result in an increased retention of amelogenin-like protein in the heterozygous female enamel as has been shown in other amelogenesis imperfecta types. (ORAL SURC ORAL MED ORAL PATHOL 1993;75:192-9) Amelogenesis imperfecta (AI) is a clinically and ge- netically diverse group of conditions that affect the enamel of teeth. Autosomal dominant, autosomal re- cessive, and X-linked modes of inheritance have been documented. Although it has been proposed that there may be as many as 14 distinct clinical forms of AI, the actual gene defects have been characterized only for X-linked AI.iF5 Current evidence suggests that two phenotypes that are classified as distinct X-linked AI types actually result from allelic muta- tions.3‘5 Delineation of AI types remains problematic be- cause there are currently no diagnostic laboratory tests readily available and because there is frequently clinical overlap between the different AI phenotypes. aAssociate Professor, Department of Pediatric Dentistry, Univer- sity of North Carolina at Chapel Hill. bSenior Lecturer, Division of Oral Biology and Pathology, Univer- sity of Queensland. CConsultant Senior Lecturer, Department of Children’s Dentistry, University of Bristol. dLecturer, Department of Oral Biology, University of Leeds. eProfessor and Director of Research, Leeds Dental Institute. Copyright @ 1993 by Mosby-Year Book, Inc, 0030-4220/93/$1.00 + .I0 l/14/47321 192 For example, hypoplastic defects appear to occur to some extent in all the major AI types.6-8 Furthermore, all three of the AI phenotypes included in most clas- sification-hypoplastic, hypocalcified, and hypomat- uration-may exhibit mineralization defects9-‘* Investigations that use linkage analysis show the gene for X-linked AI to be closely linked to the Xp22 region in several kindreds. 2-5This also is the location of the human gene for amelogenin, the principle pro- tein in developing enamel.12, l3 Further studies of X-linked AI indicate that in one kindred there is a 5 Kb deletion within the amelogenin gene3 whereas in another kindred there is a nonsense mutation as a re- sult of a single base deletion5 The effect of these mu- tations on the amelogenin protein or the specific min- eralization process of developing enamel remains un- known. Interestingly, a further kindred who exhibited X-linked AI demonstrated evidence of linkage to the long arm of the X chromosome in the Xq22-q28 re- gion.4 Taken together these findings indicate genetic heterogeneity that involves allelic mutations as well as nonallelic gene defects. There have been a number of case reports published that concern the clinical features of X-linked AI, however, little is known about the enamel ultrastruc-