FAM20A missense mutation associated with AI and gingival hyperplasia

Amelogenesis imperfecta (AI) is a group of inherited conditions manifested by enamel malformations in the absence of non-dental phenotypes, although tooth form and eruption may also be affected. We characterized for genetic studies a family exhibiting enamel defects, multiple tooth impactions with pericoronal radiolucencies, intrapulpal calcifications, and gingival hyperplasia inherited in an autosomal recessive pattern.

Objective: To use a candidate gene approach to identify the mutation responsible for the dental condition in this family.  

Methods: Intraoral examinations and dental radiographs were analyzed to define the phenotype. Mutational analyses were performed to identify potential disease-causing mutations in the coding regions and intron/exon borders of AMELX, ENAM, AMBN, FAM83H, WDR72, KLK4, MMP20, and FAM20A.

Results: Intraoral photographs of the proband showed a mixed dentition, small dental crowns with thin enamel, and yellow discoloration. Over-retained primary molars in the mandibular arch and partially erupted maxillary premolars were observed. The proband had a deep anterior overbite, a posterior cross-bite, and a class III molar relationship. Radiographically, the proband had the full-complement of permanent teeth, but eruption of the canines, mandibular premolars and molars was delayed. Some unerupted teeth with completed root formation lacked enamel, but also showed a diminished, concave occlusal surface (suggesting pre-eruptive crown resorption), intrapulpal calcifications, and an expanded dental follicle covering the crown. The same missense mutation (c992G>A; g.58853G>A; p.Gly331Asp) was identified in both FAM20A alleles in the proband and his affected sister. This sequence variation is not in the dbSNP database or 1000 Genomes Project Pilot Data. The altered glycine (G³³¹) is conserved throughout vertebrate evolution. No potential disease-causing mutations were identified in any of the other AI candidate genes.

Conclusion: We have characterized the first FAM20A missense mutation shown to cause AI with gingival hyperplasia. This study was supported by NIDCR grant DE015846.