A Recurrent FAM83H Mutation in an Extended Colombian Family and Variable Craniofacial Phenotypes

Area of Science:

• Genetics
• Dental Medicine
• Molecular Biology

Background:

• Amelogenesis imperfecta (AI) comprises rare genetic disorders impacting tooth enamel quantity and quality.
• Hypocalcified AI, characterized by weak enamel, is often linked to mutations in the FAM83H gene.
• Autosomal-dominant inheritance patterns are observed in some AI cases.

Purpose of the Study:

• To investigate the genetic cause of hypocalcified AI in a multi-generational Colombian family.
• To identify specific mutations within the FAM83H gene associated with the observed phenotype.

Main Methods:

• Candidate gene sequencing was employed to analyze the FAM83H gene in affected family members.
• A four-generation Colombian family exhibiting hypocalcified AI phenotype was recruited for the study.
• Cephalometric analyses were performed to assess skeletal and dental relationships.

Main Results:

• A recurrent nonsense mutation (NM_198488.5:c.1289C>A, p.(Ser430 *)) in the FAM83H gene was identified.
• This mutation was consistently found in affected individuals within the family.
• Cephalometric analysis indicated no correlation between anterior open bite and AI in this cohort.

Conclusions:

• The identified FAM83H gene mutation is causative for autosomal-dominant hypocalcified Amelogenesis Imperfecta in this family.
• This study contributes to the genetic landscape of Amelogenesis Imperfecta.
• Anterior open bite in the proband was determined to be an independent clinical finding.