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Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

Wang X, Zhao Y, Yang Y, Qin M - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.

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.

No MeSH data available.


Related in: MedlinePlus

The electron-density distribution of the predicted C-terminus of the wild-type and mutant LAMB3 protein.The predicted C-terminal end are shown by electrostatic potential surfaces, which are differed extensively between the wild-type and mutant LAMB3 protein (blue represents positive potential; red, negative; white, neutral).
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pone.0116514.g004: The electron-density distribution of the predicted C-terminus of the wild-type and mutant LAMB3 protein.The predicted C-terminal end are shown by electrostatic potential surfaces, which are differed extensively between the wild-type and mutant LAMB3 protein (blue represents positive potential; red, negative; white, neutral).

Mentions: After modeling the 3D structures of the wild-type and mutant LAMB3 proteins (c.3466C>T, p.Q1156X & c.1579G>A; p.V527M), we found the electron-density distribution (electrostatic surface potential) altered between the full-length and truncated LAMB3 proteins at the C-terminus (Figs. 4 and 5). The area of negative potential shown on mutant LAMB3 model was markedly enlarged in comparison to the wide-type one (Fig. 4). After 180e one (potthe distribution of three potentials differed from the wild-type as well (Fig. 5). We also performed protein structure analysis on the missense mutation (c.1579G>A; p.V527M) and the nonsense mutation (c.3466C>T, p.Q1156X), respectively. The missense mutation brought about very little change to the 3D protein structure, and the structure with only the nonsense mutation was almost the same as the one we modeled before (Figs. 4 and 5).


Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

Wang X, Zhao Y, Yang Y, Qin M - PLoS ONE (2015)

The electron-density distribution of the predicted C-terminus of the wild-type and mutant LAMB3 protein.The predicted C-terminal end are shown by electrostatic potential surfaces, which are differed extensively between the wild-type and mutant LAMB3 protein (blue represents positive potential; red, negative; white, neutral).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358960&req=5

pone.0116514.g004: The electron-density distribution of the predicted C-terminus of the wild-type and mutant LAMB3 protein.The predicted C-terminal end are shown by electrostatic potential surfaces, which are differed extensively between the wild-type and mutant LAMB3 protein (blue represents positive potential; red, negative; white, neutral).
Mentions: After modeling the 3D structures of the wild-type and mutant LAMB3 proteins (c.3466C>T, p.Q1156X & c.1579G>A; p.V527M), we found the electron-density distribution (electrostatic surface potential) altered between the full-length and truncated LAMB3 proteins at the C-terminus (Figs. 4 and 5). The area of negative potential shown on mutant LAMB3 model was markedly enlarged in comparison to the wide-type one (Fig. 4). After 180e one (potthe distribution of three potentials differed from the wild-type as well (Fig. 5). We also performed protein structure analysis on the missense mutation (c.1579G>A; p.V527M) and the nonsense mutation (c.3466C>T, p.Q1156X), respectively. The missense mutation brought about very little change to the 3D protein structure, and the structure with only the nonsense mutation was almost the same as the one we modeled before (Figs. 4 and 5).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.

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.

No MeSH data available.


Related in: MedlinePlus