A new locus for autosomal dominant amelogenesis imperfecta on chromosome 8q24.3

Abstract

Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically diverse forms of defective tooth enamel development. AI has been reported to exhibit a variety of inheritance patterns, and several loci have been identified that are associated with AI. We have performed a genome-wide scan in a large Brazilian family segregating an autosomal dominant form of AI and mapped a novel locus to 8q24.3. A maximum multipoint LOD score of 7.5 was obtained at marker D8S2334 (146,101,309 bp). The disease locus lies in a 1.9 cM (2.1 Mb) region according to the Rutgers Combined Linkage-Physical map, between a VNTR marker (at 143,988,705 bp) and the telomere (146,274,826 bp). Ten candidate genes were identified based on gene ontology and microarray-facilitated gene selection using the expression of murine orthologues in dental tissue, and examined for the presence of a mutation. However, no causative mutation was identified.

Fig. 1

Pedigree of family AMI1 segregating autosomal dominant hypomineralized amelogenesis imperfecta. Affected males and females are indicated by filled squares and circles, respectively. The proband is marked by the arrow. The genotypes of the microsatellite markers that were used to define the candidate interval are shown below each individual used in the linkage analysis screen. The black bar represents the marker haplotype that tracks with the affected status, and the grey bar indicates the marker haplotype that tracks with the unaffected status. White bars indicate marker haplotypes acquired from individuals who married into family AMI1

Fig. 2

Oral photographs of a individual V:11, b individual V:8, and c individual V:2 from family AMI1. d A dental Xray of the molars and premolars of individual V:2