Limits...
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 2.(A) Frontal clinical photograph of the 13-year-old proband. (B, C) Representative examples of enamel pitting in the proband are illustrated by the arrows in the photographs. (D) Pedigree of Family 2. Black dots indicate members recruited for this study. (E,F) ENAM exon 5 sequencing chromatogram of the proband's father (II-2) (E), and the proband (III-1) (F), revealed a single-base deletion mutation: c. 139delA, p. M47Cfs*11. (G) Panoramic radiograph of the proband.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4358960&req=5

pone.0116514.g002: Clinical and mutation analysis of Family 2.(A) Frontal clinical photograph of the 13-year-old proband. (B, C) Representative examples of enamel pitting in the proband are illustrated by the arrows in the photographs. (D) Pedigree of Family 2. Black dots indicate members recruited for this study. (E,F) ENAM exon 5 sequencing chromatogram of the proband's father (II-2) (E), and the proband (III-1) (F), revealed a single-base deletion mutation: c. 139delA, p. M47Cfs*11. (G) Panoramic radiograph of the proband.

Mentions: The proband was a 13-year-old girl who presented to our department due to the sensitivity to cold and hot stimuli. Her enamel defect was localized hypoplasia mainly involved the incisors and was particularly thin on the incisal 1/2 of maxillary anterior teeth (Fig. 2A). Her other teeth seemed normal, but when observed closely, localized enamel pitting could be seen on smooth surfaces of some premolars (Fig. 2B, 2C). No abnormality other than the thinner-than-normal layer of enamel was revealed on the radiograph (Fig. 2G). Her mother (II-1) reported the similar dental problems just like her daughter before her maxillary anterior teeth were covered with crowns.


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 2.(A) Frontal clinical photograph of the 13-year-old proband. (B, C) Representative examples of enamel pitting in the proband are illustrated by the arrows in the photographs. (D) Pedigree of Family 2. Black dots indicate members recruited for this study. (E,F) ENAM exon 5 sequencing chromatogram of the proband's father (II-2) (E), and the proband (III-1) (F), revealed a single-base deletion mutation: c. 139delA, p. M47Cfs*11. (G) Panoramic radiograph of the proband.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0116514.g002: Clinical and mutation analysis of Family 2.(A) Frontal clinical photograph of the 13-year-old proband. (B, C) Representative examples of enamel pitting in the proband are illustrated by the arrows in the photographs. (D) Pedigree of Family 2. Black dots indicate members recruited for this study. (E,F) ENAM exon 5 sequencing chromatogram of the proband's father (II-2) (E), and the proband (III-1) (F), revealed a single-base deletion mutation: c. 139delA, p. M47Cfs*11. (G) Panoramic radiograph of the proband.
Mentions: The proband was a 13-year-old girl who presented to our department due to the sensitivity to cold and hot stimuli. Her enamel defect was localized hypoplasia mainly involved the incisors and was particularly thin on the incisal 1/2 of maxillary anterior teeth (Fig. 2A). Her other teeth seemed normal, but when observed closely, localized enamel pitting could be seen on smooth surfaces of some premolars (Fig. 2B, 2C). No abnormality other than the thinner-than-normal layer of enamel was revealed on the radiograph (Fig. 2G). Her mother (II-1) reported the similar dental problems just like her daughter before her maxillary anterior teeth were covered with crowns.

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