[Genetic analysis and multidisciplinary treatment of a pedigree affected with autosomal dominant hypocalcified amelogenesis imperfecta].

Abstract

Purpose: To investigate the pathogenic gene of one Chinese family with autosomal dominant hypocalcified amelogenesis imperfecta and to report multidisciplinary treatment process for two patients from this family, so as to provide guidance for genetic counseling and clinical treatment of hereditary amelogenesis imperfecta.

Methods: The clinical data and peripheral blood of the family members were collected. Whole-exome sequencing was performed, and candidate variants were filtered out by data analysis. The identified variant was confirmed by Sanger sequencing and protein three-dimensional structure prediction.

Results: Affected members of this hereditary family exhibited yellow-brown discoloration of the dental crowns, rough tooth surfaces, and enamel erosion, consistent with hypocalcified amelogenesis imperfecta. A nonsense mutation c.1363C＞T(p.Gln455*) in exon 5 of the FAM83H gene was identified in the proband, her mother, and her sister; this mutation was predicted to cause a truncation of the FAM83H protein. This variant was not found in unaffected family members. After receiving multidisciplinary treatment based on orthodontics, the proband and her sister restored oral function and aesthetics.

Conclusions: The nonsense variant of FAM83H caused hypocalcified amelogenesis imperfecta in this study is detected for the first time in a Chinese family. The results further validate the pathogenic variant involved in FAM83H leading to amelogenesis imperfecta. Patients with amelogenesis imperfecta can restore oral function and aesthetics through various orthodontic and restorative treatments.