title: Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.
abstract: Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI). Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB), while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16) in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11) in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X) in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Qin
mesh_terms: D000293:Adolescent; D000328:Adult; D000567:Amelogenesis Imperfecta / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics*; D002648:Child; D002681:China; D003743:Dental Enamel / Q000473:pathology; D003744:Dental Enamel Hypoplasia / Q000235:genetics* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D000097794:Kalinin; C550525:ENAM protein, human