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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

Clinical and mutation analysis of Family 1.(A) Pedigree of Family 1. Black dots indicate members recruited for this study. (B) Frontal clinical photograph of the 7.5-year-old proband. (C) Frontal clinical photograph of the proband's father. (D, E) ENAM exon 7 sequencing chromatogram of an unaffected family member (II:1) (D), and the proband (III:1) (E), revealed a 19-bp insertion mutation: c.406_407insTCAAAAAAGCCGACCACAA, p.K136IfsX*16. (F) Panoramic radiograph of the proband taken at the age of 6.5.
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pone.0116514.g001: Clinical and mutation analysis of Family 1.(A) Pedigree of Family 1. Black dots indicate members recruited for this study. (B) Frontal clinical photograph of the 7.5-year-old proband. (C) Frontal clinical photograph of the proband's father. (D, E) ENAM exon 7 sequencing chromatogram of an unaffected family member (II:1) (D), and the proband (III:1) (E), revealed a 19-bp insertion mutation: c.406_407insTCAAAAAAGCCGACCACAA, p.K136IfsX*16. (F) Panoramic radiograph of the proband taken at the age of 6.5.

Mentions: The clinical phenotype of this family was typical hypoplastic pitting and horizontal grooves. The proband was a 7.5-year-old girl presenting with grooved and pitted hypoplastic enamel in her newly-erupted permanent incisors without her primary teeth being affected. The spacing of the mandibular anterior teeth was clearly secondary to the thin enamel on the crowns. Anterior crossbite was noted though the maxillary incisors have not completely erupted (Fig. 1B). Radiographic examination showed generally thin enamel especially in anterior teeth and unerupted canines. The radiographic density of the enamel was normal or similar in density to the underlying dentin. Signs of taurodontism in the first permanent molars as well as in the mandibular first primary molars could also be seen (Fig. 1F). The enamel of the proband's father showed typical horizontal grooves on the buccal and lingual/palatal surfaces (the left maxillary incisor was a removable denture). Chips were visible on the incisal edges of the maxillary incisors. No occlusal problems were found in this participant (Fig. 1C). The proband’s grandfather (I-4) had worn a maxillary and a mandibular complete denture for at least 5 years (data not available). He reported that he had dental problems similar to those of his son, indicating a dominant pattern of inheritance.


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

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

Clinical and mutation analysis of Family 1.(A) Pedigree of Family 1. Black dots indicate members recruited for this study. (B) Frontal clinical photograph of the 7.5-year-old proband. (C) Frontal clinical photograph of the proband's father. (D, E) ENAM exon 7 sequencing chromatogram of an unaffected family member (II:1) (D), and the proband (III:1) (E), revealed a 19-bp insertion mutation: c.406_407insTCAAAAAAGCCGACCACAA, p.K136IfsX*16. (F) Panoramic radiograph of the proband taken at the age of 6.5.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0116514.g001: Clinical and mutation analysis of Family 1.(A) Pedigree of Family 1. Black dots indicate members recruited for this study. (B) Frontal clinical photograph of the 7.5-year-old proband. (C) Frontal clinical photograph of the proband's father. (D, E) ENAM exon 7 sequencing chromatogram of an unaffected family member (II:1) (D), and the proband (III:1) (E), revealed a 19-bp insertion mutation: c.406_407insTCAAAAAAGCCGACCACAA, p.K136IfsX*16. (F) Panoramic radiograph of the proband taken at the age of 6.5.
Mentions: The clinical phenotype of this family was typical hypoplastic pitting and horizontal grooves. The proband was a 7.5-year-old girl presenting with grooved and pitted hypoplastic enamel in her newly-erupted permanent incisors without her primary teeth being affected. The spacing of the mandibular anterior teeth was clearly secondary to the thin enamel on the crowns. Anterior crossbite was noted though the maxillary incisors have not completely erupted (Fig. 1B). Radiographic examination showed generally thin enamel especially in anterior teeth and unerupted canines. The radiographic density of the enamel was normal or similar in density to the underlying dentin. Signs of taurodontism in the first permanent molars as well as in the mandibular first primary molars could also be seen (Fig. 1F). The enamel of the proband's father showed typical horizontal grooves on the buccal and lingual/palatal surfaces (the left maxillary incisor was a removable denture). Chips were visible on the incisal edges of the maxillary incisors. No occlusal problems were found in this participant (Fig. 1C). The proband’s grandfather (I-4) had worn a maxillary and a mandibular complete denture for at least 5 years (data not available). He reported that he had dental problems similar to those of his son, indicating a dominant pattern of inheritance.

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