title: The dentin phosphoprotein repeat region and inherited defects of dentin.
abstract: 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.
authors.affiliation: Department of Biologic and Materials SciencesUniversity of Michigan School of Dentistry1210 Eisenhower PlaceAnn ArborMichigan; Department of Pediatric DentistrySchool and Hospital of StomatologyPeking University22 South AvenueZhongguancun Haidian DistrictBeijing100081China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anthropology Pennsylvania State University University Park Pennsylvania 16802.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kawasaki
authors.affiliation: Department of Biomedical Sciences Seoul National University College of Medicine 275-1 Yongon-dong, Chongno-gu Seoul 110-768 Korea.
authors.forename: Moses
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Biologic and Materials Sciences University of Michigan School of Dentistry 1210 Eisenhower Place Ann Arbor Michigan.
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Reid
authors.affiliation: Department of Biologic and Materials Sciences University of Michigan School of Dentistry 1210 Eisenhower Place Ann Arbor Michigan.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Nunez
authors.affiliation: Department of Biomedical Sciences Seoul National University College of Medicine 275-1 Yongon-dong, Chongno-gu Seoul 110-768 Korea.
authors.forename: Murim
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Pedodontics Faculty of Dentistry Istanbul University Istanbul Turkey.
authors.forename: Figen
authors.initials: F
authors.lastname: Seymen
authors.affiliation: Department of Pedodontics Faculty of Dentistry Istanbul University Istanbul Turkey.
authors.forename: Mine
authors.initials: M
authors.lastname: Koruyucu
authors.affiliation: Department of Pedodontics Faculty of Dentistry Istanbul University Istanbul Turkey.
authors.forename: Yelda
authors.initials: Y
authors.lastname: Kasimoglu
authors.affiliation: Department of Paediatric Dentistry Women's and Children's Hospital 72 King William Road North Adelaide South Australia 5006 Australia.
authors.forename: Ninna
authors.initials: N
authors.lastname: Estrella-Yuson
authors.affiliation: Department of Pediatric Dentistry School of Dentistry University of California San Francisco California.
authors.forename: Brent P J
authors.initials: BP
authors.lastname: Lin
authors.affiliation: Department of Biologic and Materials Sciences University of Michigan School of Dentistry 1210 Eisenhower Place Ann Arbor Michigan.
authors.forename: James P
authors.initials: JP
authors.lastname: Simmer
authors.affiliation: Department of Biologic and Materials Sciences University of Michigan School of Dentistry 1210 Eisenhower Place Ann Arbor Michigan.
authors.forename: Jan C-C
authors.initials: JC
authors.lastname: Hu
keywords: Mutations; SMRT technology; osteogenesis imperfecta; tooth; whole‐exome sequencing