期刊
BIOLOGY-BASEL
卷 11, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/biology11030417
关键词
MIS-C; HLH; VUS; DOCK8
类别
资金
- Kaul Pediatric Research Institute from the Children's Hospital of Alabama, AL, USA
Children with COVID-19 have the potential to develop a novel syndrome known as MIS-C, characterized by high levels of inflammation. This study discovered that a small number of children with MIS-C carried genetic mutations, including a variant called DOCK8, which may be a risk factor for the development of this syndrome. These findings contribute to a better understanding of the mechanisms underlying MIS-C.
Simple Summary Children with a COVID-19 infection are at risk of developing a novel syndrome called multisystem inflammatory syndrome in children (MIS-C). This disease state is characterized by a high level of inflammation. It is unclear why only some children infected with SARS-CoV-2 later develop MIS-C. There may be genetic risk factors for MIS-C development, but none have previously been reported. We report genetic findings in a group of children with MIS-C. Multisystem inflammatory syndrome in children (MIS-C) affects few children previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In 2020, 45 children admitted to our hospital for MIS-C underwent genetic screening with a commercial 109-immune-gene panel. Thirty-nine children were diagnosed with MIS-C, and 25.4% of the 39 MIS-C patients harbored rare heterozygous missense mutations either in primary hemophagocytic lymphohistiocytosis (pHLH) genes (LYST, STXBP2, PRF1, UNC13D, AP3B1) or the HLH-associated gene DOCK8 (four variants). We demonstrate that foamy virus introduction of cDNA for the four DOCK8 variants into human NK-92 natural killer (NK) cells led to decreased CD107a expression (degranulation) and decreased NK cell lytic function in vitro for each variant. Heterozygous carriers of missense mutations in pHLH genes and DOCK8 may serve as risk factors for development of MIS-C among children previously infected with SARS-CoV-2.
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