title: De novo mutation in the DSPP gene associated with dentinogenesis imperfecta type II in a Japanese family.
abstract: Dentinogenesis imperfecta (DGI) type II is one of the most common dominantly inherited dentin defects, in which both the primary and permanent teeth are affected. Here, we report a Japanese family with autosomal-dominant DGI type II, including both molecular genetic defects and pathogenesis with histological analysis. Mutation analysis revealed a mutation (c.53T>A, p.V18D, g.1192T>A) involving the second nucleotide of the first codon within exon 3 of the dentin sialophosphoprotein (DSPP) gene. This mutation has previously been reported in a Korean family. Thus far, 24 allelic DSPP mutations have been reported, and this is the seventh mutation involving the DSPP V18 residue. Among those, only one other was shown to be caused by a de novo mutation, and that mutation also affected the V18 amino acid residue. The DSPP V18 residue is highly conserved among other mammalian species. These findings thus suggest that the V18 amino acid might be a sensitive mutational hot spot, playing a critical role in the pathogenesis of DGI.
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kida
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tsutsumi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shindoh
authors.forename: Hisami
authors.initials: H
authors.lastname: Ikeda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
mesh_terms: D000241:Adenosine; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D003811:Dentinogenesis Imperfecta / Q000145:classification / Q000235:genetics*; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005799:Genes, Dominant; D006801:Humans; D007564:Japan; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D012795:Sialoglycoproteins / Q000235:genetics*; D013941:Thymine; D014633:Valine / Q000235:genetics; D000099311:Dentin Sialophosphoprotein
chemical_list: D000241:Adenosine; D001224:Aspartic Acid; D003062:Codon; D016326:Extracellular Matrix Proteins; D009711:Nucleotides; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D013941:Thymine; D014633:Valine; D000099311:Dentin Sialophosphoprotein