title: MMP20 hemopexin domain mutation in amelogenesis imperfecta.
abstract: Proteolytic enzymes serve important functions during dental enamel formation, and mutations in the kallikrein 4 (KLK4) and enamelysin (MMP20) genes cause autosomal-recessive amelogenesis imperfecta (ARAI). So far, only 1 KLK4 and 3 MMP20 mutations have been reported in ARAI kindreds. To determine whether ARAI in a family with a hypomaturation-type enamel defect is caused by mutations in the genes encoding enamel proteolytic enzymes, we performed mutational analysis on candidate genes. Mutational and haplotype analyses revealed an ARAI-causing point mutation (c.910G>A, p.A304T) in exon 6 of MMP20 that results in a single amino acid substitution in the hemopexin domain. Western blot analysis showed decreased expression of the mutant protein, but zymogram analysis demonstrated that this mutant was a functional protein. The proband and an affected brother were homozygous for the mutation, and both unaffected parents were carriers. The enamel of newly erupted teeth had normal thickness, but was chalky white and became darker with age.
authors: Department of Cell and Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, 275-1 Yongon-dong, Chongno-gu, Seoul 110-768, Korea.
authors: S-K
authors: SK
authors: Lee
authors: F
authors: F
authors: Seymen
authors: H-Y
authors: HY
authors: Kang
authors: K-E
authors: KE
authors: Lee
authors: K
authors: K
authors: Gencay
authors: B
authors: B
authors: Tuna
authors: J-W
authors: JW
authors: Kim
mesh_terms: D000328:Adult; D000567:Amelogenesis Imperfecta / Q000150:complications / Q000235:genetics* / Q000473:pathology; D053523:Amelogenin / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D003743:Dental Enamel / Q000473:pathology*; D003746:Dental Enamel Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006466:Hemopexin / Q000235:genetics*; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D008297:Male; D053519:Matrix Metalloproteinase 20 / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D012016:Reference Values; D014075:Tooth Discoloration / Q000209:etiology / Q000235:genetics / Q000473:pathology
chemical_list: C507199:AMELX protein, human; D053523:Amelogenin; D003746:Dental Enamel Proteins; D006466:Hemopexin; D007610:Kallikreins; C120801:kallikrein 4; D053519:Matrix Metalloproteinase 20