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Updated: Oct 2, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
A novel FAM83H variant causes familial amelogenesis imperfecta with incomplete penetrance
Rui-Qi Bai1, Wen-Bin He2,3,4,5, Qian Peng1
1Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, Hunan, People's Republic of China.
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.
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