Combined Single Nucleotide Variants of <i>ORAI1</i> and <i>BLK</i> in a Child with Refractory Kawasaki Disease
Kawasaki disease (KD) is a systemic vasculitis with an unknown etiology affecting young children. Although intravenous immunoglobulin (IVIG) plus acetylsalicylic acid is effective in most cases, approximately 10–20% of patients do not respond to this therapy. An 8-month-old boy was admitted to a loc...
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MDPI AG
2021-05-01
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| Online Access: | https://www.mdpi.com/2227-9067/8/6/433 |
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| author | Saki Kanda Yoshimitsu Fujii Shin-ichiro Hori Taichi Ohmachi Ken Yoshimura Koichiro Higasa Kazunari Kaneko |
| author_facet | Saki Kanda Yoshimitsu Fujii Shin-ichiro Hori Taichi Ohmachi Ken Yoshimura Koichiro Higasa Kazunari Kaneko |
| author_sort | Saki Kanda |
| collection | DOAJ |
| description | Kawasaki disease (KD) is a systemic vasculitis with an unknown etiology affecting young children. Although intravenous immunoglobulin (IVIG) plus acetylsalicylic acid is effective in most cases, approximately 10–20% of patients do not respond to this therapy. An 8-month-old boy was admitted to a local hospital with the presumptive diagnosis of KD. He received IVIG twice and four series of methylprednisolone pulse therapy from the third to the tenth day of illness. Despite these treatments, his fever persisted with the development of moderate dilatations of the coronary arteries. A diagnosis of refractory KD was made, and infliximab with oral prednisolone was administered without success. Defervescence was finally achieved by cyclosporine A, an inhibitor of the signaling pathway of the calcineurin/nuclear factor of activated T cells (NFAT). Whole-genome sequencing of his deoxyribonucleic acid samples disclosed two single nucleotide variants (SNVs) in disease-susceptibility genes in Japanese KD patients, <i>ORAI1</i> (rs3741596) and <i>BLK</i> (rs2254546). In summary, the refractory nature of the present case could be explained by the presence of combined SNVs in susceptibility genes associated with upregulation of the calcineurin/NFAT signaling pathway. It may provide insights for stratifying KD patients based on the SNVs in their susceptibility genes. |
| first_indexed | 2024-03-10T11:10:09Z |
| format | Article |
| id | doaj.art-3b21479f40324add95bf3ca839c50302 |
| institution | Directory Open Access Journal |
| issn | 2227-9067 |
| language | English |
| last_indexed | 2024-03-10T11:10:09Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Children |
| spelling | doaj.art-3b21479f40324add95bf3ca839c503022023-11-21T20:50:32ZengMDPI AGChildren2227-90672021-05-018643310.3390/children8060433Combined Single Nucleotide Variants of <i>ORAI1</i> and <i>BLK</i> in a Child with Refractory Kawasaki DiseaseSaki Kanda0Yoshimitsu Fujii1Shin-ichiro Hori2Taichi Ohmachi3Ken Yoshimura4Koichiro Higasa5Kazunari Kaneko6Department of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, JapanDepartment of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, JapanDepartment of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, JapanDepartment of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, JapanDepartment of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, JapanDepartment of Genome Analysis, Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, JapanDepartment of Pediatrics, Kansai Medical University, Osaka, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, JapanKawasaki disease (KD) is a systemic vasculitis with an unknown etiology affecting young children. Although intravenous immunoglobulin (IVIG) plus acetylsalicylic acid is effective in most cases, approximately 10–20% of patients do not respond to this therapy. An 8-month-old boy was admitted to a local hospital with the presumptive diagnosis of KD. He received IVIG twice and four series of methylprednisolone pulse therapy from the third to the tenth day of illness. Despite these treatments, his fever persisted with the development of moderate dilatations of the coronary arteries. A diagnosis of refractory KD was made, and infliximab with oral prednisolone was administered without success. Defervescence was finally achieved by cyclosporine A, an inhibitor of the signaling pathway of the calcineurin/nuclear factor of activated T cells (NFAT). Whole-genome sequencing of his deoxyribonucleic acid samples disclosed two single nucleotide variants (SNVs) in disease-susceptibility genes in Japanese KD patients, <i>ORAI1</i> (rs3741596) and <i>BLK</i> (rs2254546). In summary, the refractory nature of the present case could be explained by the presence of combined SNVs in susceptibility genes associated with upregulation of the calcineurin/NFAT signaling pathway. It may provide insights for stratifying KD patients based on the SNVs in their susceptibility genes.https://www.mdpi.com/2227-9067/8/6/433<i>BLK</i>cyclosporine A<i>ORAI1</i>refractory Kawasaki diseasesingle nucleotide variant |
| spellingShingle | Saki Kanda Yoshimitsu Fujii Shin-ichiro Hori Taichi Ohmachi Ken Yoshimura Koichiro Higasa Kazunari Kaneko Combined Single Nucleotide Variants of <i>ORAI1</i> and <i>BLK</i> in a Child with Refractory Kawasaki Disease Children <i>BLK</i> cyclosporine A <i>ORAI1</i> refractory Kawasaki disease single nucleotide variant |
| title | Combined Single Nucleotide Variants of <i>ORAI1</i> and <i>BLK</i> in a Child with Refractory Kawasaki Disease |
| title_full | Combined Single Nucleotide Variants of <i>ORAI1</i> and <i>BLK</i> in a Child with Refractory Kawasaki Disease |
| title_fullStr | Combined Single Nucleotide Variants of <i>ORAI1</i> and <i>BLK</i> in a Child with Refractory Kawasaki Disease |
| title_full_unstemmed | Combined Single Nucleotide Variants of <i>ORAI1</i> and <i>BLK</i> in a Child with Refractory Kawasaki Disease |
| title_short | Combined Single Nucleotide Variants of <i>ORAI1</i> and <i>BLK</i> in a Child with Refractory Kawasaki Disease |
| title_sort | combined single nucleotide variants of i orai1 i and i blk i in a child with refractory kawasaki disease |
| topic | <i>BLK</i> cyclosporine A <i>ORAI1</i> refractory Kawasaki disease single nucleotide variant |
| url | https://www.mdpi.com/2227-9067/8/6/433 |
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