Overlapping DSPP mutations cause dentin dysplasia and dentinogenesis imperfecta.
Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders due to mutations in DSPP. Typically, the phenotype breeds true within a family. Recently, two reports showed that 3 different net -1 bp frameshift mutations early in DSPP's repeat domain caused DD, whereas 6 more 3' frameshift mutations were associated with DGI. Here we identify a DD kindred with a novel -1 bp frameshift (c.3141delC) that falls within the portion of the DSPP repeat domain previously associated solely with the DGI phenotype. This new frameshift mutation shows that overlapping DSPP mutations can give rise to either DGI or DD phenotypes. Furthermore, the consistent kindred presentation of the DD or DGI phenotype appears to be dependent on an as-yet-undescribed genetic modifier closely linked to DSPP.
McKnight
D A
DA
Craniofacial and Skeletal Diseases Branch, NIDCR, NIH, DHHS, 9000 Rockville Pike, Bldg. 30, Bethesda, MD 20892, USA.
Simmer
J P
JP
Hart
P S
PS
Hart
T C
TC
Fisher
L W
LW
D020413:3' Untranslated Regions / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D020029:Base Pairing / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003805:Dentin Dysplasia / Q000235:genetics*; D003811:Dentinogenesis Imperfecta / Q000235:genetics*; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D010375:Pedigree; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D020539:Sequence Analysis, Protein; D017384:Sequence Deletion / Q000235:genetics; D012694:Serine / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics*; D000099311:Dentin Sialophosphoprotein
D020413:3' Untranslated Regions; D001224:Aspartic Acid; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D012694:Serine; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein