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Combined Single Nucleotide Variants of ORAI1 and BLK 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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224368/ https://www.ncbi.nlm.nih.gov/pubmed/34064199 http://dx.doi.org/10.3390/children8060433 |
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author | Kanda, Saki Fujii, Yoshimitsu Hori, Shin-ichiro Ohmachi, Taichi Yoshimura, Ken Higasa, Koichiro Kaneko, Kazunari |
author_facet | Kanda, Saki Fujii, Yoshimitsu Hori, Shin-ichiro Ohmachi, Taichi Yoshimura, Ken Higasa, Koichiro Kaneko, Kazunari |
author_sort | Kanda, Saki |
collection | PubMed |
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, ORAI1 (rs3741596) and BLK (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. |
format | Online Article Text |
id | pubmed-8224368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82243682021-06-25 Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease Kanda, Saki Fujii, Yoshimitsu Hori, Shin-ichiro Ohmachi, Taichi Yoshimura, Ken Higasa, Koichiro Kaneko, Kazunari Children (Basel) Case Report 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, ORAI1 (rs3741596) and BLK (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. MDPI 2021-05-21 /pmc/articles/PMC8224368/ /pubmed/34064199 http://dx.doi.org/10.3390/children8060433 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Case Report Kanda, Saki Fujii, Yoshimitsu Hori, Shin-ichiro Ohmachi, Taichi Yoshimura, Ken Higasa, Koichiro Kaneko, Kazunari Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease |
title | Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease |
title_full | Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease |
title_fullStr | Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease |
title_full_unstemmed | Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease |
title_short | Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease |
title_sort | combined single nucleotide variants of orai1 and blk in a child with refractory kawasaki disease |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224368/ https://www.ncbi.nlm.nih.gov/pubmed/34064199 http://dx.doi.org/10.3390/children8060433 |
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