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Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children
IMPORTANCE: Clinical, genetic, and laboratory characteristics of Middle Eastern patients with multisystem inflammatory syndrome in children (MIS-C) have not yet been documented. OBJECTIVE: To assess the genetic and clinical characteristics of patients with MIS-C of primarily Arab and Asian origin. D...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157271/ https://www.ncbi.nlm.nih.gov/pubmed/35639375 http://dx.doi.org/10.1001/jamanetworkopen.2022.14985 |
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author | Abuhammour, Walid Yavuz, Lemis Jain, Ruchi Abu Hammour, Khawla Al-Hammouri, Ghalia F. El Naofal, Maha Halabi, Nour Yaslam, Sawsan Ramaswamy, Sathishkumar Taylor, Alan Wafadari, Deena Alsarhan, Ali Khansaheb, Hamda Deesi, Zulfa Omar Varghese, Rupa Murthy Uddin, Mohammed Al Suwaidi, Hanan Al-Hammadi, Suleiman Alkhaja, Abdulmajeed AlDabal, Laila Mohamed Loney, Tom Nowotny, Norbert Al Khayat, Abdulla Alsheikh-Ali, Alawi Abou Tayoun, Ahmad |
author_facet | Abuhammour, Walid Yavuz, Lemis Jain, Ruchi Abu Hammour, Khawla Al-Hammouri, Ghalia F. El Naofal, Maha Halabi, Nour Yaslam, Sawsan Ramaswamy, Sathishkumar Taylor, Alan Wafadari, Deena Alsarhan, Ali Khansaheb, Hamda Deesi, Zulfa Omar Varghese, Rupa Murthy Uddin, Mohammed Al Suwaidi, Hanan Al-Hammadi, Suleiman Alkhaja, Abdulmajeed AlDabal, Laila Mohamed Loney, Tom Nowotny, Norbert Al Khayat, Abdulla Alsheikh-Ali, Alawi Abou Tayoun, Ahmad |
author_sort | Abuhammour, Walid |
collection | PubMed |
description | IMPORTANCE: Clinical, genetic, and laboratory characteristics of Middle Eastern patients with multisystem inflammatory syndrome in children (MIS-C) have not yet been documented. OBJECTIVE: To assess the genetic and clinical characteristics of patients with MIS-C of primarily Arab and Asian origin. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter cohort study was conducted from September 1, 2020, to August 31, 2021, in the United Arab Emirates and Jordan. Forty-five patients with MIS-C and a matched control group of 25 healthy children with a confirmed SARS-CoV-2 infection status were recruited. Whole exome sequencing in all 70 participants was performed to identify rare, likely deleterious variants in patients with MIS-C and to correlate genetic findings with the clinical course of illness. EXPOSURES: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Fever, organ system complications, laboratory biomarkers, whole exome sequencing findings, treatments, and clinical outcomes were measured. The Mann-Whitney U test was used to assess the association between genetic variants and MIS-C attributes. The Fisher exact test was used to compute the genetic burden in MIS-C relative to controls. RESULTS: A total of 45 patients with MIS-C (23 [51.1%] male; 30 [66.7%] of Middle Eastern origin; mean [SD] age, 6.7 [3.6] years) and 25 controls (17 [68.0%] male; 24 [96.0%] of Middle Eastern origin; mean [SD] age 7.4 [4.0] years) participated in the study. Key inflammatory markers were significantly dysregulated in all patients with MIS-C. Mucocutaneous and gastrointestinal manifestations were each reported in 36 patients (80.0%; 95% CI, 66.1%-89.1%), cardiac findings were reported in 22 (48.9%; 95% CI, 35.0%-63.0%), and neurologic findings were reported in 14 (31.1%; 95% CI, 19.5%-45.6%). Rare, likely deleterious heterozygous variants in immune-related genes, including TLR3, TLR6, IL22RA2, IFNB1, and IFNA6, were identified in 19 patients (42.2%; 95% CI, 29.0%-56.7%), of whom 7 had multiple variants. There was higher enrichment of genetic variants in patients relative to controls (29 vs 3, P < .001). Patients with those variants tended to have earlier disease onset (7 patients [36.8%; 95% CI, 19.1%-58.9%] with genetic findings vs 2 [7.7%; 95% CI, 2.1%-24.1%] without genetic findings were younger than 3 years at onset) and resistance to treatment (8 patients [42.1%; 95% CI, 23.1%-63.7%] with genetic findings vs 3 patients [11.5%; 95% CI, 4.0%-29.0%] without genetic findings received 2 doses of intravenous immunoglobulin). CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that rare, likely deleterious genetic variants may contribute to MIS-C disease. This finding paves the way for additional studies with larger, diverse populations to fully characterize the genetic contribution to this new disease entity. |
format | Online Article Text |
id | pubmed-9157271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-91572712022-06-16 Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children Abuhammour, Walid Yavuz, Lemis Jain, Ruchi Abu Hammour, Khawla Al-Hammouri, Ghalia F. El Naofal, Maha Halabi, Nour Yaslam, Sawsan Ramaswamy, Sathishkumar Taylor, Alan Wafadari, Deena Alsarhan, Ali Khansaheb, Hamda Deesi, Zulfa Omar Varghese, Rupa Murthy Uddin, Mohammed Al Suwaidi, Hanan Al-Hammadi, Suleiman Alkhaja, Abdulmajeed AlDabal, Laila Mohamed Loney, Tom Nowotny, Norbert Al Khayat, Abdulla Alsheikh-Ali, Alawi Abou Tayoun, Ahmad JAMA Netw Open Original Investigation IMPORTANCE: Clinical, genetic, and laboratory characteristics of Middle Eastern patients with multisystem inflammatory syndrome in children (MIS-C) have not yet been documented. OBJECTIVE: To assess the genetic and clinical characteristics of patients with MIS-C of primarily Arab and Asian origin. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter cohort study was conducted from September 1, 2020, to August 31, 2021, in the United Arab Emirates and Jordan. Forty-five patients with MIS-C and a matched control group of 25 healthy children with a confirmed SARS-CoV-2 infection status were recruited. Whole exome sequencing in all 70 participants was performed to identify rare, likely deleterious variants in patients with MIS-C and to correlate genetic findings with the clinical course of illness. EXPOSURES: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Fever, organ system complications, laboratory biomarkers, whole exome sequencing findings, treatments, and clinical outcomes were measured. The Mann-Whitney U test was used to assess the association between genetic variants and MIS-C attributes. The Fisher exact test was used to compute the genetic burden in MIS-C relative to controls. RESULTS: A total of 45 patients with MIS-C (23 [51.1%] male; 30 [66.7%] of Middle Eastern origin; mean [SD] age, 6.7 [3.6] years) and 25 controls (17 [68.0%] male; 24 [96.0%] of Middle Eastern origin; mean [SD] age 7.4 [4.0] years) participated in the study. Key inflammatory markers were significantly dysregulated in all patients with MIS-C. Mucocutaneous and gastrointestinal manifestations were each reported in 36 patients (80.0%; 95% CI, 66.1%-89.1%), cardiac findings were reported in 22 (48.9%; 95% CI, 35.0%-63.0%), and neurologic findings were reported in 14 (31.1%; 95% CI, 19.5%-45.6%). Rare, likely deleterious heterozygous variants in immune-related genes, including TLR3, TLR6, IL22RA2, IFNB1, and IFNA6, were identified in 19 patients (42.2%; 95% CI, 29.0%-56.7%), of whom 7 had multiple variants. There was higher enrichment of genetic variants in patients relative to controls (29 vs 3, P < .001). Patients with those variants tended to have earlier disease onset (7 patients [36.8%; 95% CI, 19.1%-58.9%] with genetic findings vs 2 [7.7%; 95% CI, 2.1%-24.1%] without genetic findings were younger than 3 years at onset) and resistance to treatment (8 patients [42.1%; 95% CI, 23.1%-63.7%] with genetic findings vs 3 patients [11.5%; 95% CI, 4.0%-29.0%] without genetic findings received 2 doses of intravenous immunoglobulin). CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that rare, likely deleterious genetic variants may contribute to MIS-C disease. This finding paves the way for additional studies with larger, diverse populations to fully characterize the genetic contribution to this new disease entity. American Medical Association 2022-05-31 /pmc/articles/PMC9157271/ /pubmed/35639375 http://dx.doi.org/10.1001/jamanetworkopen.2022.14985 Text en Copyright 2022 Abuhammour W et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License. |
spellingShingle | Original Investigation Abuhammour, Walid Yavuz, Lemis Jain, Ruchi Abu Hammour, Khawla Al-Hammouri, Ghalia F. El Naofal, Maha Halabi, Nour Yaslam, Sawsan Ramaswamy, Sathishkumar Taylor, Alan Wafadari, Deena Alsarhan, Ali Khansaheb, Hamda Deesi, Zulfa Omar Varghese, Rupa Murthy Uddin, Mohammed Al Suwaidi, Hanan Al-Hammadi, Suleiman Alkhaja, Abdulmajeed AlDabal, Laila Mohamed Loney, Tom Nowotny, Norbert Al Khayat, Abdulla Alsheikh-Ali, Alawi Abou Tayoun, Ahmad Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children |
title | Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children |
title_full | Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children |
title_fullStr | Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children |
title_full_unstemmed | Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children |
title_short | Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children |
title_sort | genetic and clinical characteristics of patients in the middle east with multisystem inflammatory syndrome in children |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157271/ https://www.ncbi.nlm.nih.gov/pubmed/35639375 http://dx.doi.org/10.1001/jamanetworkopen.2022.14985 |
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