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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 3.(A) Pedigree of Family 3. Black dots indicate members recruited for this study. (B) Frontal clinical photograph of the 14.5-year-old proband. (C, D) Lateral clinical photographs of the proband's mother. (E, F) LAMB3 exon 23 sequencing chromatogram of an unaffected family member (II:2) (E), and the proband (III:1) (F), revealed a nonsense mutation: c.3466C>T, p.Q1156X. (G) Panoramic radiograph of the proband.
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pone.0116514.g003: Clinical and mutation analysis of Family 3.(A) Pedigree of Family 3. Black dots indicate members recruited for this study. (B) Frontal clinical photograph of the 14.5-year-old proband. (C, D) Lateral clinical photographs of the proband's mother. (E, F) LAMB3 exon 23 sequencing chromatogram of an unaffected family member (II:2) (E), and the proband (III:1) (F), revealed a nonsense mutation: c.3466C>T, p.Q1156X. (G) Panoramic radiograph of the proband.

Mentions: In family 3, four family members were available (II-1, II-2, III-1 and III-9). The proband was a 14.5-year-old girl presenting with general hypoplasia in all permanent teeth. Her mother, who was the source of information concerning the pedigree and dental status of unexamined individuals, reported that affected family members had dental problems similar to those of the proband (Fig. 3A). The mother had lost most of her molars except for two upper teeth, with a total of 18 teeth still remaining (Fig. 3C and D). The girl displayed a distinctive pattern of enamel defects featuring deep irregular grooves and pits (Fig. 3B). No anterior open bite but a mild edge-to-edge occlusion was found in this proband. Her panoramic radiograph showed severe generalized enamel hypoplasia, but the enamel was generally more radiopaque than dentin. Excessive root canal calcification was evident in all erupted molars (Fig. 3G). No medical history of skin fragility or other syndromes was reported in this family.


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 3.(A) Pedigree of Family 3. Black dots indicate members recruited for this study. (B) Frontal clinical photograph of the 14.5-year-old proband. (C, D) Lateral clinical photographs of the proband's mother. (E, F) LAMB3 exon 23 sequencing chromatogram of an unaffected family member (II:2) (E), and the proband (III:1) (F), revealed a nonsense mutation: c.3466C>T, p.Q1156X. (G) Panoramic radiograph of the proband.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0116514.g003: Clinical and mutation analysis of Family 3.(A) Pedigree of Family 3. Black dots indicate members recruited for this study. (B) Frontal clinical photograph of the 14.5-year-old proband. (C, D) Lateral clinical photographs of the proband's mother. (E, F) LAMB3 exon 23 sequencing chromatogram of an unaffected family member (II:2) (E), and the proband (III:1) (F), revealed a nonsense mutation: c.3466C>T, p.Q1156X. (G) Panoramic radiograph of the proband.
Mentions: In family 3, four family members were available (II-1, II-2, III-1 and III-9). The proband was a 14.5-year-old girl presenting with general hypoplasia in all permanent teeth. Her mother, who was the source of information concerning the pedigree and dental status of unexamined individuals, reported that affected family members had dental problems similar to those of the proband (Fig. 3A). The mother had lost most of her molars except for two upper teeth, with a total of 18 teeth still remaining (Fig. 3C and D). The girl displayed a distinctive pattern of enamel defects featuring deep irregular grooves and pits (Fig. 3B). No anterior open bite but a mild edge-to-edge occlusion was found in this proband. Her panoramic radiograph showed severe generalized enamel hypoplasia, but the enamel was generally more radiopaque than dentin. Excessive root canal calcification was evident in all erupted molars (Fig. 3G). No medical history of skin fragility or other syndromes was reported in this family.

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