PMC4358960_01
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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Anterior crossbite was noted though the maxillary incisors have not completely erupted (Fig. 1B). Signs of taurodontism in the first permanent molars as well as in the mandibular first primary molars could also be seen (Fig. 1F). No occlusal problems were found in this participant (Fig. 1C).
PMC4358960_02
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.
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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).
PMC4358960_03
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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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). Excessive root canal calcification was evident in all erupted molars (Fig. 3G).
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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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). 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).
The electron-density distribution of C-terminus of the wild-type and mutant LAMB3 protein after 180  rotation.. After 180  rotation, the difference of the electron-density distribution between the wild-type and mutant LAMB3 protein is shown.
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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). After 180e one (potthe distribution of three potentials differed from the wild-type as well (Fig. 5). 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).