PMC8691729_01
PMC8691729_02
Identification of mutations by DNA sequencing and relative quantification of MVK exon 9 and 11 expression in the patient and her parents. The heterozygous MVK mutation c.769T>A (p.Phe257Ile) in the patient was inherited from her mother (blue arrows), and the exon 11 deletion was inherited from her father (red arrows). Fold-change in expression of MVK exons 9 and 11 measured using quantitative RT-PCR. GAPDH expression was used to normalize target gene expression. The relative expression of each gene was calculated as the log2 of 2- Ct values. MVK, mevalonate kinase; RT-PCR, reverse transcription PCR; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
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Under the suspicion of congenital disease that causes systemic inflammation, whole-exome sequencing (WES, Methods in Supplementary Material) was performed, which revealed that the patient carried a heterozygous mutation of c.769T>A (p.Phe257Ile) in MVK ( Table 1 ;  Figure 1 ;  Methods in Supplementary Material ). In the result of WES, heterozygous deletionat exon11 of MVK gene was suspected with lower depth than other exons.A real-time polymerase chain reaction (PCR) assay was performed to analyze the expression of MVK in the patient and parents, which revealed decreased expression of exon 11 in the patient and father ( Figure 1  and  Methods in Supplementary Material ).
Clinical course of the patient. At the time of diagnosis, leukocytosis was prominent, and CRP was above the normal range. After the 1st HCT, the WBC count was normalized, and CRP and total bilirubin levels decreased to a normal range and showed alternate increases and decreases during chemotherapy. WBC, white blood cell; CRP, C-reactive protein; tBil, total bilirubin; mPD, methylprednisolone; PD, prednisolone; MA, mevalonic aciduria; HCT, hematopoietic stem cell transplantation; AML, acute myeloid leukemia; CTx, chemotherapy.
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Her fever and levels of inflammatory markers began decreasing in response to intravenous methylprednisolone at 30 mg/kg/day for 3 days but reappeared repeatedly when the drug was tapered or changed to oral prednisolone ( Figure 2 ).
PMC8691729_03
Results of work-up at the diagnosis of acute myeloid leukemia. (A) Bone marrow smears taken from the patient (myeloblast: black arrows). (B) Representative karyotype of the blast was 45, XX, -7. (C) Fluorescence in situ hybridization of the 7q deletion showing monosomy 7.
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Human Cytokine/Chemokine Magnetic Bead Panel (Merck KGaA Inc., Darmstadt, Germany), and the levels of cytokines such as Il-1beta, IL-6, and TNFalpha, which are involved in systemic inflammation, were found to be decreased remarkably ( Figure 3 ). However, recipient chimerism increased by up to 34% at day 42; therefore, the immunosuppressant was stopped, and a donor lymphocyte infusion was performed. Results from the bone marrow biopsy showed hypercellularity of the bone marrow tissue, with an increase in the number of myeloblasts ( Figure 3A ). Figure 3B ). Fluorescence in situ hybridization (FISH) revealed 7q deletion in myeloblasts, showing monosomy 7 ( Figure 3C ).
PMC8691729_04