FAM83H mutations cause ADHCAI and alter intracellular protein localization.

Abstract

Mutations in a family with sequence similarity 83 member H (FAM83H) cause autosomal-dominant hypocalcification amelogenesis imperfecta (ADH CAI). All FAM83H ADHCAI-causing mutations terminate translation or shift the reading frame within the specific exon 5 segment that encodes from Ser(287) to Glu(694). Mutations near Glu(694) cause a milder, more localized phenotype. We identified disease-causing FAM83H mutations in two families with ADHCAI: family 1 (g.3115C>T, c.1993 C>T, p.Q665X) and family 2 (g.3151C>T, c.2029 C>T, p.Q677X). We also tested the hypothesis that truncation mutations alter the intracellular localization of FAM83H. Wild-type FAM83H and p.E694X mutant FAM83H fused to green fluorescent protein (GFP) localized in the cytoplasm of HEK293T cells, but the mutant FAM83H proteins (p.R325X, p.W460X, and p.Q677X) fused to GFP localized mainly in the nucleus with slight expression in the cytoplasm. We conclude that nuclear targeting of the truncated FAM83H protein contributes to the severe, generalized enamel phenotype.

• Authors: S-K Lee, K-E Lee, T-S Jeong, Y-H Hwang, S Kim, J C-C Hu, J P Simmer, J-W Kim
• Journal: Journal of dental research (J Dent Res) Vol. 90 Issue 3 Pg. 377-81 (Mar 2011) ISSN: 1544-0591 [Electronic] United States
• PMID: 21118793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense
• Dental Enamel Proteins
• FAM83H protein, human
• Proteins

Topics

• Amelogenesis Imperfecta (genetics, pathology)
• Cell Nucleus (metabolism)
• Child
• Chromosomes, Human, Pair 8 (genetics)
• Codon, Nonsense
• DNA Mutational Analysis
• Dental Enamel (pathology)
• Dental Enamel Proteins (genetics)
• Female
• Genes, Dominant
• HEK293 Cells
• Humans
• Korea
• Male
• Pedigree
• Protein Transport (genetics)
• Proteins (genetics)