PMC7417345_01
(A) Clinical findings. Exposed root surfaces of the teeth 33-43 due to severe gingivitis and periodontitis in an age of 24 years. (B) Orthopantomogram. General alveolar bone loss caused by severe chronic periodontitis. The wisdom teeth 18 and 38 are partially erupted and the mandibular anterior teeth are stabilized by a retainer.
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F1
At the age of 18 years severe gingivitis and chronic periodontitis with subsequent significant retraction of gingiva and alveolar bone resorption were diagnosed (Figures 1A,B).
Identification of start filled loss mutation in CD70. (A) Pedigree of the family in which a homozygous start loss mutation in CD70 was identified. The genotype of each individual is indicated. The black circle represents the affected individual. (B) DNA electropherograms show the region containing the mutation in CD70 in the family. The homozygous missense mutation is indicated by an arrow.
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F2
Familial segregation analysis confirmed that the patient was homozygous for the mutation, while parents were heterozygous and the healthy brother was homozygous for the wild type (Figure 2).
Analysis of CD27 and CD70 expressions in B and T cells of patient. (A) Representative dot-plot FACS analyses of isotype (upper panels), CD27, and CD70 (lower panels) stainings of control and patient CD4 T cell blasts were depicted. Cells were analysed at day 8 of culture after PHA stimulation. (B) Percentages of CD27 and CD70 positive CD4 T cells blasts of 6 healthy donors and the patient are shown in dot plot graph (left and right panels, respectively). Data are normalised on isotype staining. (C) Flow cytometry analyses of CD19 and CD70 expression in PBMCs of control and parents. (D, left panel), immunoblots for CD70 and Ku70 protein expression in control and parents lysates of lymphoblastoid cell line (LCL). Right panel, representative histogram overlay flow cytometry analysis corresponding to CD70 (filled) and isotype (unfilled) stainings of activated control and parents LCLs. (E) Representative dot-plot FACS analyses of CD27 and CD70 stainings of control, parents and patient T cell blasts were depicted. Cells were analyzed at day 15 of culture after PHA stimulation. (A-D) Data were obtained from FACS analysis after cell-specific staining. Data shown are representative of 2 independent experiments and were performed using Flowjo software.
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F3
Following genetic testing, flow cytometry analyses of patient activated T cell blasts and B cells confirmed absence of CD70 expression (Figures 3A-C). B cells in blood, in a EBV-derived lymphoblastoid cell line (LCL) and activated T cell blasts (Figures 3D,E). Both parents had no history of frequent or severe infections.