Alternative titles; symbols
HGNC Approved Gene Symbol: IFNAR1
Cytogenetic location: 21q22.11 Genomic coordinates (GRCh38): 21:33,324,395-33,359,864 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 21q22.11 | Immunodeficiency 106, susceptibility to viral infections | 619935 | Autosomal recessive | 3 |
The IFNAR1 gene encodes a membrane protein that, together with IFNAR2 (602376), forms the type I alpha/beta IFN receptor. Activation of the IFNAR by IFN-alpha and IFN-beta leads to tyrosine phosphorylation of several genes that form a downstream signaling pathway. IFNAR1 interacts with TYK2 (176941), and IFNAR2 interacts with JAK1 and STAT proteins. Activation of this signaling pathway results in the expression of IFN-stimulated genes (ISGs) that mainly play a role in controlling viral infections (summary by Khanmohammadi et al., 2022).
Novick et al. (1994) described a universal ligand-binding receptor for human interferons alpha and interferon beta. Sarkar and Gupta (1984) showed that gamma-interferon binds to a separate receptor that is carried by WISH cells (a human amnion cell line). The gene for the receptor was designated also IFNAR.
Lutfalla et al. (1992) detected 11 exons in the IFNAR gene.
Alpha-type antiviral protein is a factor that mediates specific interferon inhibition of virus replication. According to studies of mouse-man hybrid clones, the locus determining this protein is carried on chromosome 21 (Tan et al., 1973). Tan et al. (1974) made observations of dosage effect in monosomy-21 and trisomy-21 cells, which supported assignment of the locus to chromosome 21. This character was also called interferon sensitivity (IS). Chany et al. (1975) showed that trisomy-21 cells have increased interferon sensitivity. Trisomy-16 cells have reduced sensitivity. This might suggest the presence on chromosome 16 of a regulator of mouse antiviral protein.
In trisomy-21 fibroblasts, Epstein and Epstein (1976) demonstrated an exaggerated response to both classic (virus-induced) and immune (phytohemagglutinin-induced) forms of interferon. This suggested that despite their physical and antigenic differences the antiviral expression of the 2 interferons is mediated by the same genetic locus. A line trisomic for the distal part of the long arm 21q21-qter also demonstrated increased response, indicating that the AVP gene is located on this part of chromosome 21. Lin et al. (1980) demonstrated that the genes for soluble SOD (147450) and interferon sensitivity are syntenic in the mouse and on chromosome 16.
Raziuddin et al. (1984) showed that the receptors for alpha- and beta-interferons are specified by chromosome 21. It was presumed that separate genes encoded the alpha- and beta-interferon receptors.
Langer et al. (1990) sublocalized the IFNAR gene to 21q22.1-q22.2 by hybridization of (32)P-labeled recombinant interferon-alpha/beta receptor with human-hamster somatic cell hybrids containing various fragments of human chromosome 21. By in situ hybridization, Lutfalla et al. (1990) refined the assignment to 21q22.1. Lutfalla et al. (1992) further refined the localization by pulsed field gel electrophoresis and its linkage to adjacent markers. They compared the exon structure of the IFNAR gene with that of the genes for receptors of the cytokine/growth hormone/prolactin/interferon receptor family and concluded that they have a common origin and have diverged from the immunoglobulin superfamily with which they share a common ancestor.
Revel et al. (1976) showed that antibody to a cell surface component coded by human chromosome 21 inhibited the action of interferon. This suggested that antiviral protein is an interferon receptor. See 147570, 147640, 147660 for a discussion of the gamma, beta, and alpha interferons, respectively. De Clercq et al. (1976) concluded that it is not a cell membrane receptor for interferon that is encoded by chromosome 21.
Cellular responses to cytokines involve cross-communication through their respective receptors (summary by Takaoka et al., 2000). The IFNs alpha, beta, and gamma mediate innate immune responses to viral infection through IFNAR1/IFNAR2 (602376) for IFNA and IFNB, and IFNGR1 (107470)/IFNGR2 (147569) for IFNG. Stimulation of these receptors activates Janus protein kinases (e.g., JAK1, 147795 and JAK2, 147796), which leads to the tyrosine phosphorylation of STAT1 (600555) and STAT2 (600556). Although the IFN receptors are expressed at low levels in cells, they may be clustered in the cell membrane to permit efficient signal transduction.
Using mouse embryonic fibroblasts (MEFs) from IFNAR1- and IFNGR1-deficient mice, Takaoka et al. (2000) observed that the STAT1-mediated DNA-binding activity and the antiviral response to IFNG in IFNAR-null MEFs but not to IFNA in IFNGR-null MEFs are impaired. Restoration of the IFNG response requires constitutive subthreshold IFNA/IFNB signaling and an intact IFNAR1 capable of interacting with STAT1 after tyrosine phosphorylation. Immunoblot analysis showed that IFNAR1 coimmunoprecipitated with the nonligand-binding component, IFNGR2, of the IFNGR complex in wildtype MEFs but less well in IFNB-null MEFs. Immunoblot analysis also demonstrated that the IFN receptor components are exclusively localized in the caveolar membrane fractions (see CAV1; 601047) where there is a concentration of cytoplasmically oriented signaling molecules.
In the type I interferon receptor, TYK2 (176941) associates with the IFNAR1 receptor subunit and positively influences ligand binding to the receptor complex. Ragimbeau et al. (2003) found that TYK2 was required for stable cell surface expression of IFNAR1 in human fibrosarcoma cells. In the absence of TYK2, IFNAR1 was exported to the plasma membrane but then accumulated in endocytic organelles. TYK2 coexpression prevented intracellular accumulation of IFNAR1 by restraining its constitutive internalization, and thus stabilized it at the cell surface.
Essers et al. (2009) showed that in response to treatment of mice with Ifn-alpha, hematopoietic stem cells (HSCs) efficiently exit G0 and enter an active cell cycle. HSCs respond to Ifn-alpha treatment by the increased phosphorylation of Stat1 (600555) and Akt1 (164730), the expression of Ifn-alpha target genes, and the upregulation of stem cell antigen-1 (Sca1, also known as Ly6a, present only in mouse). HSCs lacking the Ifn-alpha/beta receptor (Ifnar), Stat1, or Sca1 are insensitive to Ifn-alpha stimulation, demonstrating that Stat1 and Sca1 mediate Ifn-alpha-induced HSC proliferation. Although dormant HSCs are resistant to the antiproliferative chemotherapeutic agent 5-fluoro-uracil, HSCs pretreated (primed) with Ifn-alpha and thus induced to proliferate are efficiently eliminated by 5-fluoro-uracil exposure in vivo. Conversely, HSCs chronically activated by Ifn-alpha are functionally compromised and are rapidly outcompeted by nonactivatable Ifnar-null cells in competitive repopulation assays. Whereas chronic activation of the Ifn-alpha pathway in HSCs impairs their function, acute Ifn-alpha treatment promotes the proliferation of dormant HSCs in vivo.
Zhou et al. (2012) reported that IFNAR1 contains a target sequence for the microRNA MIR1231 (617040) in its 3-prime UTR.
In 2 unrelated patients with immunodeficiency-106 (IMD106; 619935) manifest as adverse reaction to MMR and yellow fever vaccinations, Hernandez et al. (2019) identified homozygous or compound heterozygous mutations in the IFNAR1 gene (107450.0001-107450.0003). There were 2 splice site and 1 nonsense mutations, suggesting a loss-of-function effect. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. None were present in the 1000 Genomes Project or gnomAD databases. Western blot analysis of patient-derived fibroblast and lymphoid cells showed complete lack of IFNAR1 expression, suggesting nonsense-mediated mRNA decay of the mutant transcripts. Patient cells showed impaired type I interferon (IFN) signaling, as evidenced by lack of phosphorylation of the downstream targets STAT1 (600555) and STAT2 (600556) in response to stimulation. Patient cells also had impaired type I IFN immunity to viruses compared to controls. Transduction of patient cells with wildtype IFNAR1 was able to rescue these defects.
In a 21-month-old boy with IMD106 manifest as a fatal hyperinflammatory response to MMR vaccination, Gothe et al. (2022) identified a homozygous nonsense mutation in the IFNAR1 gene (Q308X; 107450.0005). The mutation, which was found by whole-exome sequencing, was not present in the gnomAD database. There was no detectable IFNAR1 protein in patient-derived cells, consistent with a complete loss of function. In vitro functional expression studies of patient cells showed impaired signaling responses to stimulation with alpha or beta-interferon (see, e.g., IFNA2, 147562), but intact responses to gamma-interferon (IFNG; 147570). Patient cells were susceptible to infection with the picornavirus EMCV and the Zika virus, and this defect could be rescued by treatment with IFNG, but not IFNA2. Expression of wildtype IFNAR1 in patient cells restored induction of interferon-stimulated genes (ISGs) and the overall antiviral state in response to IFNA2. The patient developed features of hemophagocytic lymphohistiocytosis (HLH) following MMR vaccination in infancy, but vaccine-strain viral particles were not detected, consistent with 'sterile autoinflammation' and suggesting an immunoregulatory role for IFNAR1 towards other cytokines.
In 2 members (P1 and P2) of a consanguineous Arab family with IMD106, Bastard et al. (2021) identified a homozygous deletion in the IFNAR1 gene (107450.0006). The mutation, which was found by analysis of copy number variants and confirmed by Sanger sequencing, segregated with the phenotype in the family. It was not present in multiple public databases, including gnomAD. Analysis of patient cells showed that the deletion resulted in aberrant splicing predicted to generate a protein with a C-terminal truncation lacking residues known to be critical for the interaction of IFNAR1 with TYK2 (176941). Patient-derived fibroblasts showed low levels of IFNAR1 mRNA, suggesting nonsense-mediated mRNA decay, although a truncated protein was expressed on the cell surface. Patient cells showed no signaling response or induction of interferon-stimulated gene (ISG) expression in response to stimulation with IFNA2 (147562) or IFNB (147640). The cellular response to IFNG was normal. The signaling defects could be rescued by expression of wildtype IFNAR1. Patient cells also showed enhanced susceptibility to infection and increased viral replication when exposed to several viruses, including HSV1 and measles, compared to controls. In this family, P1 died of HSV1-associated encephalitis, whereas P2 had a less severe phenotype with recurrent viral infections, suspected to include HSV1 and mumps. The findings highlighted a critical role for IFNAR1 immunity and the type I interferon response to protect against HSV1 infection in the CNS.
In 7 patients from 5 unrelated families of western Polynesian origin with IMD106, Bastard et al. (2022) identified a homozygous nonsense mutation in the IFNAR1 gene (E386X; 107450.0007). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The mutation was found once in the heterozygous state in the gnomAD database. The carrier frequency of the mutation was estimated at 1.25% in the Samoan population, with lesser frequencies in some, but not all, other Pacific Island populations. In vitro functional studies in HEK293 cells transfected with the E386X mutation showed presence of a truncated IFNAR1 protein that was not detected at the plasma membrane. Transfected cells showed a total absence of luciferase reporter activity in response to IFNA2, consistent with a loss of function and complete IFNAR1 deficiency. Cells derived from 1 patient (P3) showed no detectable IFNAR1 at the cell surface, absence of a signaling response to stimulation with IFNA2, an overall defective response to type I IFNs, and impaired induction of interferon-stimulated genes (ISGs). Expression of wildtype IFNAR1 rescued these defects.
In a 3-year-old girl, born of consanguineous Iranian parents, with IMD106 manifest as a severe inflammatory response to SARS-CoV-2 infection resulting in death, Abolhassani et al. (2022) identified a homozygous deletion in the IFNAR1 gene (107450.0008) resulting in frameshift. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Patient cells were not available for study, but in vitro expression studies of cells transfected with the mutation showed almost undetectable IFNAR1 surface expression as well as impaired functional signaling response to stimulation with certain interferons. These findings were consistent with complete IFNAR1 deficiency, and indicated that a type I IFN response is essential for protective immunity against SARS-CoV-2 in the respiratory tract. This patient was also reported by Zhang et al. (2022) as patient P12 in a study of an international cohort of 112 children less than 16 years of age who were hospitalized for COVID-19 pneumonia.
Listeria monocytogenes (Lm) induces a cytosolic signaling cascade that results in expression of IFNB, a cytokine critical in viral defense. Auerbuch et al. (2004) found that Ifnar1-deficient mice were much more resistant to Lm infection than wildtype mice, suggesting that induction of Ifnb during Lm intracytosolic growth leads to enhanced bacterial survival. Resistance to Lm infection in Ifnar1-deficient mice was associated with an increase in the number of Cd11b (ITGAM; 120980)-positive cells producing Tnf (191160). Auerbuch et al. (2004) proposed that intracytosolic Lm induces Ifnb expression, thereby suppressing Tnf-producing phagocytic cells at sites of bacterial growth.
Blank et al. (2016) found that exposure to synthetic double-stranded RNA, a prototype RNA virus, or recombinant type I IFN induced cognitive impairment and mood changes in mice. Ifnb activated Ifnar1 expressed on brain endothelia and epithelia, which released Cxcl10 (147310) into brain parenchyma, compromising neuronal function. Mice lacking Cxcl10 or its receptor, Cxcr3 (300574), were protected from depressive behavior and impaired learning and memory following Ifnb treatment. Blank et al. (2016) concluded that brain endothelial and epithelial cells play an important role in communication between the central nervous system and the immune system and that IFNAR1 is engaged in a tissue-specific manner during sickness behavior. They proposed that the CXCL10-CXCR3 axis is a target for treatment of behavioral changes during virus infection and type I IFN therapy.
In a 9-year-old boy (P1), born of consanguineous Iranian parents, with immunodeficiency-106 (IMD106; 619935) manifest as adverse reaction to the MMR vaccination, Hernandez et al. (2019) identified a homozygous A-to-G transition in intron 5 of the IFNAR1 gene (c.674-2A-G, NM_000629), resulting in aberrant splicing. Analysis of patient-derived fibroblasts showed 3 aberrant transcripts: about 60% resulting in premature termination (Val225AlafsTer228), about 30 to 40% resulting in an in-frame deletion (Val225_Pro232del), and a trace amount that introduced a premature stop codon (Thr224_Val225insGluSerThrTer). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutation was not found in the 1000 Genomes Project or gnomAD databases. DNA from a similarly affected deceased sib was not available. Western blot analysis of patient-derived fibroblast and lymphoid cells showed complete lack of IFNAR1 expression, suggesting nonsense-mediated mRNA decay. Patient cells showed impaired type 1 interferon (IFN) signaling, as evidenced by lack of phosphorylation of the downstream targets STAT1 (600555) and STAT2 (600556) in response to stimulation. Patient cells also had impaired type 1 IFN immunity to viruses compared to controls. Transduction of patient cells with wildtype IFNAR1 was able to rescue these defects. The patient presented at about 12 months of age with disseminated vaccine-strain measles after vaccination with MMR. He had fever, neurologic symptoms consistent with encephalitis, and leukocytosis in the CSF. He had previously received hepatitis B virus, BCG, and influenza vaccines without adverse effect. Antibodies against measles and mumps were at the low limits of normal, whereas responses to pneumococcal and hepatitis B were normal. He had frequent upper respiratory infections, but had normal development and was in good health at 9 years of age. A sister had died in infancy of meningoencephalitis after receiving MMR vaccine.
Khanmohammadi et al. (2022) reported that the Iranian boy (P1) identified by Hernandez et al. (2019) developed severe COVID-19 respiratory infection requiring hospitalization at age 13 years. Treatment with gamma-interferon (IFNG; 147570) resulted in clinical improvement. This report indicated that patients with IMD106 are also susceptible to severe and life-threatening COVID-19 infections, likely due to the impaired type I IFN response.
In a 14-year-old girl (P2), born of unrelated Brazilian parents, with immunodeficiency-106 (IMD106; 619935) manifest as adverse reaction to yellow fever vaccination, Hernandez et al. (2019) identified compound heterozygous mutations in the IFNAR1 gene : a G-to-A transition in intron 5 of the IFNAR1 gene (c.674-1G-A, NM_000629), resulting in aberrant splicing, and a c.783G-A transition in exon 6, resulting in a trp261-to-ter (W261X; 107450.0003) substitution. Analysis of patient-derived fibroblasts showed 3 aberrant transcripts: about 60% resulting in premature termination (Val225AlafsTer228), about 30 to 40% resulting in an in-frame deletion (Val225_Pro232del), and a trace amount that introduced a premature stop codon (Thr224_Val225insGluSerThrTer). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutations were not found in the 1000 Genomes Project or gnomAD databases. Western blot analysis of patient-derived fibroblast and lymphoid cells showed complete lack of IFNAR1 expression, suggesting nonsense-mediated mRNA decay. Patient cells showed impaired type 1 interferon (IFN) signaling, as evidenced by lack of phosphorylation of the downstream targets STAT1 (600555) and STAT2 (600556) in response to stimulation. Patient cells also had impaired type 1 IFN immunity to viruses compared to controls. Transduction of patient cells with wildtype IFNAR1 was able to rescue these defects. The patient was healthy until age 12 years, when she developed fever, encephalitis, acute renal and hepatic failure, and leukocytosis following vaccination for yellow fever. She made a full recovery and was healthy at age 14. She had previously received 2 MMR vaccines and oral live poliovirus and BCG in early childhood without incident. She developed neutralizing antibodies to yellow fever virus in levels associated with seroprotection, as well as seropositivity to measles, rubella, diphtheria, and tetanus.
For discussion of the c.783G-A transition (c.783G-A, NM_000629) in exon 6 of the IFNAR1 gene, resulting in a trp261-to-ter (W261X) substitution, that was found in compound heterozygous state in a patient with immunodeficiency-106 (IMD106; 619935) manifest as adverse reaction to yellow fever vaccination by Hernandez et al. (2019), see 107450.0002.
In a boy, born of consanguineous Saudi parents, with immunodeficiency-106 (IMD106; 619935) manifest as early-onset disseminated CMV viremia, Hoyos-Bachiloglu et al. (2017) identified a homozygous intragenic deletion in the IFNAR1 gene (c.1671_1821del, NM_000629). The variant resulted in the addition of 46 novel residues to the C-terminal end of the protein (p.557GluextTer46). Whole-exome sequencing also identified a homozygous loss-of-function mutation in the IFNGR2 gene (147569.0007), consistent with a diagnosis of immunodeficiency-28 (IMD28; 614889). The variants, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were present in heterozygous state in each unaffected parent. In vitro functional expression studies using patient-derived fibroblasts showed impaired response to stimulation with gamma-IFN and a defect in the IFN type II signaling pathway presumably caused by the IFNGR2 gene, as well as impaired downstream signaling after stimulation with alpha-IFN, indicating a defect in the IFN type I signaling pathway. These findings of likely digenic inheritance were consistent with the patient's atypical presentation for IMD28: in addition to mycobacteriosis, he had CMV viremia and Streptococcus viridans bacteremia. The latter features were thought to result from the IFNAR1 variant and decreased type I interferon signaling through the IFNAR receptor.
In a 21-month-old boy with immunodeficiency-106 (IMD106; 619935) manifest as a fatal hyperinflammatory response to MMR vaccination, Gothe et al. (2022) identified a homozygous c.922C-T transition in the IFNAR1 gene, resulting in a gln308-to-ter (Q308X) substitution in the third extracellular domain. The mutation, which was found by whole-exome sequencing, was not present in the gnomAD database. There was no detectable IFNAR1 protein in patient-derived cells, consistent with a complete loss of function. In vitro functional expression studies of patient cells showed impaired signaling responses to stimulation with alpha or beta-interferon (see, e.g., IFNA2, 147562), but intact responses to gamma-interferon (IFNG; 147570). Patient cells were susceptible to infection with the picornavirus EMCV and the Zika virus, and this defect could be rescued by treatment with IFNG, but not IFNA2. Expression of wildtype IFNAR1 in patient cells restored induction of interferon-stimulated genes (ISGs) and the overall antiviral state in response to IFNA2. The patient developed features of hemophagocytic lymphohistiocytosis (HLH) following MMR vaccination in infancy, but vaccine-strain viral particles were not detected, consistent with 'sterile autoinflammation' and suggesting an immunoregulatory role for IFNAR1 towards other cytokines. The patient developed encephalopathy and died at 21 months of age, about 6 months after presentation.
In 2 members (P1 and P2) of a consanguineous Arab family with immunodeficiency-106 (IMD106; 619935), Bastard et al. (2021) identified a homozygous 1,675-bp deletion (chr2.g.34,726,420_34,728,094del, GRCh37) in the IFNAR1 gene that removed intron 10, the coding sequence of exon 11, and 239 basepairs of the 3-prime UTR. The mutation, which was found by analysis of copy number variants and confirmed by Sanger sequencing, segregated with the phenotype in the family. It was not present in multiple public databases, including gnomAD. Analysis of patient cells showed that the deletion resulted in aberrant splicing predicted to generate a protein with a C-terminal truncation lacking residues known to be critical for the interaction of IFNAR1 with TYK2 (176941). Patient-derived fibroblasts showed low levels of IFNAR1 mRNA, suggesting nonsense-mediated mRNA decay, although a truncated protein was expressed on the cell surface. Patient cells showed no signaling response or induction of interferon-stimulated gene (ISG) expression in response to stimulation with IFNA2 (147562) or IFNB (147640). The cellular response to IFNG (147570) was normal. The signaling defects could be rescued by expression of wildtype IFNAR1. Patient cells also showed enhanced susceptibility to infection and increased viral replication when exposed to several viruses, including HSV1 and measles, compared to controls. In vitro functional studies in transfected HEK293 cells showed expression of a mutant protein with a truncated C terminus that was expressed normally at the plasma membrane, but was unable to interact with TYK2. In this family, P1 died of HSV1-associated encephalitis, whereas P2 had a less severe phenotype with recurrent viral infections, suspected to include HSV1 and mumps. P1 received MMR vaccination and experienced only a fever that resolved spontaneously. P2 was not vaccinated with MMR, since a sib (P3) died at 12 months of age after an adverse reaction to MMR vaccination; DNA from P3 was not available. The findings highlighted a critical role for IFNAR1 immunity and the type I interferon response to protect against HSV1 infection in the CNS.
In 7 patients from 5 unrelated families of western Polynesian origin with immunodeficiency-106 (IMD106; 619935), Bastard et al. (2022) identified a homozygous c.1156G-T transversion in the IFNAR1 gene, resulting in a glu386-to-ter (E386X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The mutation was found once in the heterozygous state in the gnomAD database. The carrier frequency of the mutation was estimated at 1.25% in the Samoan population, with lesser frequencies in some, but not all, other Pacific Island populations. In vitro functional studies in HEK293 cells transfected with the E386X mutation showed presence of a truncated IFNAR1 protein that was not detected at the plasma membrane. Transfected cells showed a total absence of luciferase reporter activity in response to IFNA2 (147562), consistent with a loss of function and complete IFNAR1 deficiency. Cells derived from 1 patient (P3) showed no detectable IFNAR1 at the cell surface, absence of a signaling response to stimulation with IFNA2, an overall defective response to type I IFNs, and impaired induction of interferon-stimulated genes (ISGs). Expression of wildtype IFNAR1 rescued these defects. Six of the 7 patients had acute hyperinflammatory reactions to MMR vaccination.
In a 3-year-old girl, born of consanguineous Iranian parents, with immunodeficiency-106 (IMD106; 619935), Abolhassani et al. (2022) identified a homozygous 4,394-bp intragenic deletion (chr21:34,719,302_34,723,696) in the IFNAR1 gene, resulting in the deletion of exons 7 and 8. The deletion was predicted to result in a frameshift and premature termination before the transmembrane domain (His263fsTer14) (NM_000629), likely resulting in a complete loss of function. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Patient cells were not available for study, but in vitro expression studies of cells transfected with the mutation showed almost undetectable IFNAR1 surface expression as well as impaired functional signaling response to stimulation with certain interferons. These findings were consistent with complete IFNAR1 deficiency. The patient had a history of chronic sinusitis, oral thrush, and mucormycosis of the nose and paranasal sinuses, but showed no adverse reaction to vaccination with live attenuated vaccine (LAV), including BCG, oral polio, and MMR vaccination. At age 3 years, she presented with a severe SARS-CoV-2 infection complicated by pneumonia and multisystem inflammatory syndrome in children (MIS-C), resulting in death due to cardiorespiratory failure.
Zhang et al. (2022) reported the patient of Abolhassani et al. (2022) as patient P12 in a study of an international cohort of 112 children less than 16 years of age who were hospitalized for COVID-19 pneumonia. Zhang et al. (2022) did not identify any other children with mutations in IFNAR1 in their study.
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