Clinical And Genetic Studies Of A Chinese Family With Amelogenesis Imperfecta

Objective: Amelogenesis imperfecta(AI)is a single gene genetic disease caused by multiple genes,mainly manifested as enamel defects,with a wide range of penetrance.FAM83 H is reported to be involved in AI.The purpose of this study was to investigate the genetic causes of incomplete penetrance AI in a 4-generation Chinese family,and to provide a theoretical basis for elucidating the pathogenesis of AI.Methods: The clinical characteristics of the family were summarized through investigation and clinical examination,and the pedigree was drawn to analyze the genetic characteristics.Whole-exome sequencing was performed on two patients with AI,and putative disease-related variants were validated by Sanger sequencing.Bioinformatics analysis was performed by polyphen-2,Mutation Taster,SIFT and other software,and in vitro functional analysis was performed at the cellular level to determine the pathogenicity of the mutations.Results: We identified a novel heterozygous nonsense variant of FAM83H(NM＿198488: c.1975G>T,p.Glu659Ter);in vitro functional analysis showed that this mutant produced mislocalized proteins and was deleterious.Surprisingly,the clinical manifestations of each of the 4 individuals carrying this variant were different,with one carrier appearing to be completely asymptomatic for AI.Conclusion: Our findings expand the variant spectrum for FAM83 H and the phenotypic spectrum for FAM83H-associated AI and suggest that FAM83H-mediated AI exhibits incomplete penetrance.