PMC4302247_01
(a) Pedigree of family 1. The 'plus' symbol indicates individuals recruited for this study. (b) DNA sequencing chromatogram of the PCR amplification products from the proband (III:2) of family 1. Wild-type (top) and the mutated sequences are shown in the chromatogram. Red arrow indicates the location of the mutation (c.3357_3358insC, p.Met1120Hisfs*40). (c) Frontal clinical photo of the proband taken at the age of 2 years 1 month. (d) Clinical photo of left mandibular deciduous second molar of the proband taken at the age of 3 years 2 months. (e) Pedigree of family 2. The 'plus' symbol indicates individuals recruited for this study. (f) DNA sequencing chromatogram of the PCR amplification products from the proband (III:1) of family 2. Wild-type (top) and the mutated sequences are shown in the chromatogram. Red arrow indicates the location of the mutation (c.3463_3475del, p.Glu1155Thrfs*51). (g) Frontal clinical photo of the proband taken at the age of 8 years 7 months. (h, i) Lateral clinical photos of the father (II:3) of the proband. Hypoplastic grooves in the maxillary left first premolar and right canine indicated by black arrows. (j) Alignment of the human wild-type LAMB3 (NP_000219.2) C-terminus sequence with the predicted truncated proteins of families 1 and 2. Black bar above the sequence indicates sequence encoded by exon 22. Sequences with underline indicate novel sequences by truncating mutations.
cge0087-0090-f1.jpg
PMC4302247_02_cge0087-0090-f1.jpg
fig01
However, close examination of the father of the proband revealed hypoplastic grooves in several teeth (Fig. 1e-i). The mutation in family 2 (c.3463_3475delGAGCAGATCCGTG) would also escape NMD because of its location in the last exon producing a truncated protein with 50 novel amino acids replacing the C-terminal 18 amino acids of the wild-type LAMB3 (p.Glu1155fs*51) (Fig. 1J). This small replacement would explain the phenotypic variation in family 2 (Fig. 1j).
PMC4302247_02
(a) Pedigree of family 1. The 'plus' symbol indicates individuals recruited for this study. (b) DNA sequencing chromatogram of the PCR amplification products from the proband (III:2) of family 1. Wild-type (top) and the mutated sequences are shown in the chromatogram. Red arrow indicates the location of the mutation (c.3357_3358insC, p.Met1120Hisfs*40). (c) Frontal clinical photo of the proband taken at the age of 2 years 1 month. (d) Clinical photo of left mandibular deciduous second molar of the proband taken at the age of 3 years 2 months. (e) Pedigree of family 2. The 'plus' symbol indicates individuals recruited for this study. (f) DNA sequencing chromatogram of the PCR amplification products from the proband (III:1) of family 2. Wild-type (top) and the mutated sequences are shown in the chromatogram. Red arrow indicates the location of the mutation (c.3463_3475del, p.Glu1155Thrfs*51). (g) Frontal clinical photo of the proband taken at the age of 8 years 7 months. (h, i) Lateral clinical photos of the father (II:3) of the proband. Hypoplastic grooves in the maxillary left first premolar and right canine indicated by black arrows. (j) Alignment of the human wild-type LAMB3 (NP_000219.2) C-terminus sequence with the predicted truncated proteins of families 1 and 2. Black bar above the sequence indicates sequence encoded by exon 22. Sequences with underline indicate novel sequences by truncating mutations.
cge0087-0090-f1.jpg
PMC4302247_02_cge0087-0090-f1.jpg
fig01
However, close examination of the father of the proband revealed hypoplastic grooves in several teeth (Fig. 1e-i). The mutation in family 2 (c.3463_3475delGAGCAGATCCGTG) would also escape NMD because of its location in the last exon producing a truncated protein with 50 novel amino acids replacing the C-terminal 18 amino acids of the wild-type LAMB3 (p.Glu1155fs*51) (Fig. 1J). This small replacement would explain the phenotypic variation in family 2 (Fig. 1j).