Clinical and Genetic Outcomes in a Complex Amelogenesis Imperfecta Patient

Objectives: 1) Obtain medical/dental history of a 14-year-old male previously diagnosed with AI (UAB-SOD); 2) perform a comprehensive clinical (intra-/extra-oral) evaluation; 3) consent the patient for genetic studies; 4) collect saliva and blood samples for DNA isolation; 5) isolate genomic DNA; and 6) perform selective candidate AI gene mutational analysis on four genes.
Methods: Informed consent was obtained with IRB approval. Panoramic/cephalometric radiographs were taken. Saliva was collected (Norgen Biotek kit) and DNA isolated. Mutational analysis of exons/intron boundaries for the selected AI candidate genes, WDR72(MIM613214), MMP20(MIM604629), KLK4(MIM603767) and FAM20A(MIM611062), was performed by PCR amplification and bidirectional Sanger sequencing. Data was analyzed using the UCSC Genome Browser with potential alterations, mutations or single-nucleotide polymorphisms (SNPs), identified by comparison to the HapMap Project database.
Results: Intraoral examination revealed macroglossia, generalized yellow-stained dentition, abnormal dental spacing and Curve of Spee, large anterior open-bite and mild tongue thrust. Mutational analysis revealed no disease-causing alterations in tested genes. However, several SNPs were found: three in WDR72(rs17730281, rs60404950, and rs35258188) and a splice variant in KLK4 (rs73042387). The two MMP20 SNPs identified were in exon 6 (rs1784424/rs1784423) and the single FAM20A SNP was located in exon 11(rs2907373).
Conclusions: The tested genes WDR72, MMP20, KLK4 and FAM20A have all been associated with autosomal recessive forms of AI. However, we have excluded these genes from a causal role related to the AI proband presenting a de novo case tested in this study. Additional AI candidate genes are currently being evaluated.