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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...

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Autores principales: Kanda, Saki, Fujii, Yoshimitsu, Hori, Shin-ichiro, Ohmachi, Taichi, Yoshimura, Ken, Higasa, Koichiro, Kaneko, Kazunari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
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.
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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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