The dentin phosphoprotein repeat region and inherited defects of dentin.

TitleThe dentin phosphoprotein repeat region and inherited defects of dentin.
Publication TypeJournal Article
Year of Publication2016
AuthorsYang, J, Kawasaki, K, Lee, M, Reid, BM, Nunez, SM, Choi, M, Seymen, F, Koruyucu, M, Kasimoglu, Y, Estrella-Yuson, N, Lin, BPJ, Simmer, JP, Hu, JC-C
JournalMol Genet Genomic Med
Date Published2016 Jan

Nonsyndromic dentin defects classified as type II dentin dysplasia and types II and III dentinogenesis imperfecta are caused by mutations in DSPP (dentin sialophosphoprotein). Most reported disease-causing DSPP mutations occur within the repetitive DPP (dentin phosphoprotein) coding sequence. We characterized the DPP sequences of five probands with inherited dentin defects using single molecule real-time (SMRT) DNA sequencing. Eight of the 10 sequences matched previously reported DPP length haplotypes and two were novel. Alignment with known DPP sequences showed 32 indels arranged in 36 different patterns. Sixteen of the 32 indels were not represented in more than one haplotype. The 25 haplotypes with confirmed indels were aligned to generate a tree that describes how the length variations might have evolved. Some indels were independently generated in multiple lines. A previously reported disease-causing DSPP mutation in Family 1 was confirmed and its position clarified (c.3135delC; p.Ser1045Argfs*269). A novel frameshift mutation (c.3504_3508dup; p.Asp1170Alafs*146) caused the dentin defects in Family 2. A COL1A2 (c.2027G>A or p.Gly676Asp) missense mutation, discovered by whole-exome sequencing, caused the dentin defects in Family 3. We conclude that SMRT sequencing characterizes the DPP repeat region without cloning and can improve our understanding of normal and pathological length variations in DSPP alleles.

Alternate JournalMol Genet Genomic Med
PubMed ID26788535
PubMed Central IDPMC4707025
Grant ListR01 CA094025 / CA / NCI NIH HHS / United States
R01 DE015846 / DE / NIDCR NIH HHS / United States
U54 HG006504 / HG / NHGRI NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States