Ontology highlight
ABSTRACT: Background
Amelogenesis imperfecta (AI) is known to be a monogenic genetic disease caused by a variety of genes demonstrating a wide spectrum of penetrance. FAM83H is reported to be involved in AI: however, whether FAM83H causes AI with incomplete penetrance is unclear.Methods
Whole-exome sequencing was performed on two patients with AI, and putative disease-related variants were validated by Sanger sequencing. Bioinformatic and in vitro functional analyses were performed to functionally characterize the identified disease-causing variants.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 six individuals carrying this variant were different, with one carrier appearing to be completely asymptomatic for AI.Conclusion
Our findings expand the variant spectrum for FAM83H and the phenotypic spectrum for FAM83H-associated AI and suggest that FAM83H-mediated AI exhibits incomplete penetrance.
SUBMITTER: Bai RQ
PROVIDER: S-EPMC9000937 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
Molecular genetics & genomic medicine 20220225 4
<h4>Background</h4>Amelogenesis imperfecta (AI) is known to be a monogenic genetic disease caused by a variety of genes demonstrating a wide spectrum of penetrance. FAM83H is reported to be involved in AI: however, whether FAM83H causes AI with incomplete penetrance is unclear.<h4>Methods</h4>Whole-exome sequencing was performed on two patients with AI, and putative disease-related variants were validated by Sanger sequencing. Bioinformatic and in vitro functional analyses were performed to func ...[more]