PMC9663835_01
(A) Intraoral view of the patient in 2017. The marginal and attached gingiva were fiery red, with swelling and bleeding on contact. (B) Changes in the white blood cell, neutrophil, and lymphocyte counts over 6 weeks. The patient's neutrophil counts appeared to cycle between 200/muL and 1,500/muL, with the lymphocyte counts showing an inverse cycle pattern. (C) DNA sequence analysis of ELANE. The patient carries two spontaneous mutations. As both forward and reverse sequences can be used for verification in Sanger sequencing, the bases in the peak diagram may be the reverse complementary sequence of the detected bases. For instance, in c.180T > G, T > G is shown as A > C in the peak diagram.
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F1
The initial examination revealed that the marginal and attached gingiva was fiery red, swollen, and bled on contact (Figure 1A). Mutational analyses of the patient's sample revealed two substitutions in the 180th base (T to G), causing the amino acid substitution p.I60M, and in the 182nd base (C to G), causing the amino acid substitution p.A61G in exon2 (Figure 1C). The evaluations of neutrophil count revealed a slight fluctuation between 200-500/muL during the first 3 weeks, which increased to 1,500/muL on the 25th day, before starting the following cycle with a greater amplitude (Figure 1B). As shown in Supplementary Figure S1, her neutrophil and WBC counts increased to normal after 3 days of G-CSF administration.
Follow-up examination in 2018. (A) Intraoral view showing redness, gingiva swelling and recession, irregular tooth alignment, and serious occlusion disorder. (B) Panoramic radiograph showing general disappearance of the lamina dura and complete horizontal absorption of the alveolar bone to 1/2-2/3 of the root length. The alveolar bone loss of 14, 16, 24, 25, and 46 involved the apical roots. (C) Periodontal chart. 93% bleeding on probing, mean PD: 4.2 mm. PD, probing depth.
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F2
A timeline with relevant examination, diagnosis, and treatment information is presented in Supplementary Figure S2. Superficial dentin caries was observed on the occlusal surfaces of teeth 37 and 47 (Figures 2A,C). Panoramic radiography revealed generalized severe horizontal bone loss (Figure 2B).
(A) Intraoral view in the Hospital of Stomatology, Sun-Yat sen University in 2022. After 5 years of follow-up, the gingival swelling and redness were reduced. (B) Panoramic radiograph showing general horizontal bone loss of 1/3-2/3 of the root length. (C) Periodontal chart. Specialized periodontal examination record of the patient after the 5-year follow-up. 50% bleeding on probing, mean PD: 3.9 mm. PD, probing depth.
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F3
In contrast with the first visit in 2018, the bleeding on probing (50% in 2022 versus 93% in 2018) had decreased and the probing depth (mean PD: 3.9 mm in 2022 versus mean PD: 4.2 mm in 2018) had lessened considerably (Figure 3).
Ribbon diagrams of neutrophil elastase. (A) Position (red) of residues Ile60 and Ala61. (B) H-bonds between residues Ile60 and Ala61 and their substrate Phe64. (C) Changed H-bonds in NE mutant I60M, A61G (the present case). While three H-bonds remained between residues 60 and 61 and Phe64, the bond lengths increased, indicating weakened connections. (D) Phe64 lost two H-bonds with Arg60. (SCN, with a synchronous mutation of GFI1). (E) Phe64 obtained an additional H-bond with Thr60 (SCN). (F) Phe64 lost two H-bonds with Val60 (overlapping between SCN and CyN). Partial tertiary structures were deleted to show the variants and adjacent residues in the ribbon diagrams. The color codes for the molecules and bonds are as follows: carbon, pale cyan; oxygen, red; nitrogen, blue; sulfur, yellow; H-bond, yellow. PD, probing depth.
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F4
The intra-molecular interactions around the mutant amino acids are depicted in Figure 4.