Open AccessA novel FAM83H variant causes familial amelogenesis imperfecta with incomplete penetrance
Author(s) -
Bai RuiQi,
He WenBin,
Peng Qian,
Shen SuHui,
Yu QianQian,
Du Juan,
Tan YueQiu,
Wang YueHong,
Liu BinJie
Publication year - 2022
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1902
Subject(s) - penetrance , exome sequencing , sanger sequencing , amelogenesis imperfecta , biology , genetics , exome , phenotype , gene , mutation , medicine , enamel paint , dentistry
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.