case_images: PMC9366043_01
case_images: (A) Sanger sequencing of the FAS gene (c.857G > A, p.G286E) germlinemutation of patients (left: DNA of patient's peripheral blood; right: DNA of patient's nail). (B) Sanger sequencing of father's FAS gene. (C) Sanger sequencing of mother's FAS gene. (D) Crystal structure of the FAS/FADD death domain complex (3ezq.1.A). (E) A hydrogen bond is formed between amino acids 286G and 289E; a hydrogen bond is formed between amino acid 286G and 290A. (F) A total of two hydrogen bonds are formed between amino acids 286E and 289E; A hydrogen bond is formed between amino acid 286E and 290A. The green and red squares in panels (E,F) show the difference of hydrogen bond formation between wildtype and the mutation.
case_images: fped-10-868193-g001.jpg
case_images: PMC9366043_01_fped-10-868193-g001.jpg
case_images: F1
case_images: We identified novel spontaneous germline heterozygous missense mutations on the FAS gene (c.857G > A, p.G286E) in exon 9 (Figures 1A-C), causing an amino acid exchange and difference of hydrogen bond formation (Figures 1D-F).
case_images: (A) A representative dot plot analysis of CD4-CD8-TCRalphabeta + cells gated in the CD3 + cell fraction showed elevated DNT ratio compared to a healthy control. The DNT ratio of the patient decreased after sirolimus treatment. (B) A representative dot polt analysis of CD25 + foxP3 + cells gated in the CD4 + cell fraction showed decreased Treg ratio compared to a healthy control. The Treg ratio of the patient increased after sirolimus treatment.
case_images: fped-10-868193-g002.jpg
case_images: PMC9366043_01_fped-10-868193-g002.jpg
case_images: F2
case_images: After 4 weeks of rapamycin treatment, DNTs/CD3 + and DNTs/lymphocyte were decreased from 6.8 to 4.44% and 4.69 to 3.34%, respectively (Figure 2A). Treg increased to a normal level from 2.5 to 4.12% (Figure 2B).
case_images: (A) Changes in patient's hemoglobulin during sirolimus therapy. (B) Changes in patient's neutrophil count during sirolimus therapy. (C) Changes in patient's platelet count during sirolimus therapy. (D) Changes in DNTs during sirolimus therapy.
case_images: fped-10-868193-g003.jpg
case_images: PMC9366043_01_fped-10-868193-g003.jpg
case_images: F3
case_images: Subsequently, the patient's platelets and hemoglobulin levels improved rapidly (Figures 3A-C). Moreover, the DNT ratio continuously decreased during sirolimus application (Figure 3D).