title: Novel MMP20 and KLK4 Mutations in Amelogenesis Imperfecta.
abstract: In order to achieve highly mineralized tooth enamel, enamel proteinases serve the important function of removing the remaining organic matrix in the mineralization and maturation of the enamel matrix. Mutations in the kallikrein 4 (KLK4), enamelysin (MMP20), and WDR72 genes have been identified as causing hypomaturation enamel defects in an autosomal-recessive hereditary pattern. In this report, 2 consanguineous families with a hypomaturation-type enamel defect were recruited, and mutational analysis was performed to determine the molecular genetic etiology of the disease. Whole exome sequencing and autozygosity mapping identified novel homozygous mutations in the KLK4 (c.620_621delCT, p.Ser207Trpfs*38) and MMP20 (c.1054G>A, p.Glu352Lys) genes. Further analysis on the effect of the mutations on the translation, secretion, and function of KLK4 and MMP20 revealed that mutant KLK4 was degraded intracellularly and became inactive while mutant MMP20 was expressed at a normal level but secreted only minimally with proteolytic function.
authors.affiliation: Department of Pedodontics, Istanbul University, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Seymen
authors.affiliation: Department of Cell and Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: J-C
authors.initials: JC
authors.lastname: Park
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: K-E
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: H-K
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: D-S
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Pedodontics, Istanbul University, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Koruyucu
authors.affiliation: Department of Pedodontics, Istanbul University, Istanbul, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Gencay
authors.affiliation: Department of Pedodontics, Istanbul University, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Bayram
authors.affiliation: Department of Pedodontics, Istanbul University, Istanbul, Turkey.
authors.forename: E B
authors.initials: EB
authors.lastname: Tuna
authors.affiliation: Department of Cell and Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Lee
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea Department of Molecular Genetics & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea pedoman@snu.ac.kr.
authors.forename: J-W
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000567:Amelogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics*; D015153:Blotting, Western; D002648:Child; D003241:Consanguinity; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007610:Kallikreins / Q000235:genetics*; D053519:Matrix Metalloproteinase 20 / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011862:Radiography, Panoramic; D017422:Sequence Analysis, DNA
chemical_list: D007610:Kallikreins; C120801:kallikrein 4; C507111:MMP20 protein, human; D053519:Matrix Metalloproteinase 20
keywords: enamel; enamelysin; hereditary; hypomaturation; matrix; proteinase