Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review
The neurological complications of coronavirus disease 2019 (COVID-19) can range from simple tremors and dystonia to features of encephalopathy. Toll-like receptor 7 (TLR7) belongs to a family of innate immune receptors responsible for viral RNA detection (such as SARS-CoV-2) and immune response init...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1268035/full |
| _version_ | 1827630878020337664 |
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| author | Ahmed Noor Eddin Mohammed Al-Rimawi Feham Peer-Zada Khalid Hundallah Amal Alhashem Amal Alhashem |
| author_facet | Ahmed Noor Eddin Mohammed Al-Rimawi Feham Peer-Zada Khalid Hundallah Amal Alhashem Amal Alhashem |
| author_sort | Ahmed Noor Eddin |
| collection | DOAJ |
| description | The neurological complications of coronavirus disease 2019 (COVID-19) can range from simple tremors and dystonia to features of encephalopathy. Toll-like receptor 7 (TLR7) belongs to a family of innate immune receptors responsible for viral RNA detection (such as SARS-CoV-2) and immune response initiation. TLR7 loss of function variants have been previously reported as genetic risk factors for severe COVID-19 infection in young patients with no comorbidities. In this case, we report a pediatric patient who developed severe long-term neurological deterioration following his COVID-19 infection. Presenting first to the clinic with episodic dystonia and finger spasticity, the patient’s condition rapidly deteriorated with a significant drop in the Glasgow Coma Scale (GCS). Despite improvement following initial treatment with rituximab and intravenous immunoglobulin, the patient’s symptoms relapsed, and GCS further dropped to 3/15. Serial brain magnetic resonance imaging scans revealed diffuse parenchymal atrophy, ventricular enlargement, and spinal cord thickening. Autoimmune investigations were negative but clinical whole genome sequencing prioritized four gene variants, the most significant of which was a novel frameshift null variant of the X chromosomal TLR7 gene (c.1386_1389dup, p.[His464Ilefs*7]). This case illustrates a role for TLR7 in long-term COVID-19 complications and highlights that TLR7 deficiency in the future may be addressed as a therapeutic measure. |
| first_indexed | 2024-03-09T14:13:14Z |
| format | Article |
| id | doaj.art-e7764d1fcc2f43a6a98f9c92704c992b |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-09T14:13:14Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-e7764d1fcc2f43a6a98f9c92704c992b2023-11-29T05:53:23ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-11-011410.3389/fneur.2023.12680351268035Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature reviewAhmed Noor Eddin0Mohammed Al-Rimawi1Feham Peer-Zada2Khalid Hundallah3Amal Alhashem4Amal Alhashem5College of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaDivision of Pediatric Neurology, Department of Pediatrics, Prince Sultan Medical Military City, Riyadh, Saudi ArabiaCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaDivision of Genetic and Metabolic Medicine, Department of Pediatrics, Prince Sultan Medical Military City, Riyadh, Saudi ArabiaThe neurological complications of coronavirus disease 2019 (COVID-19) can range from simple tremors and dystonia to features of encephalopathy. Toll-like receptor 7 (TLR7) belongs to a family of innate immune receptors responsible for viral RNA detection (such as SARS-CoV-2) and immune response initiation. TLR7 loss of function variants have been previously reported as genetic risk factors for severe COVID-19 infection in young patients with no comorbidities. In this case, we report a pediatric patient who developed severe long-term neurological deterioration following his COVID-19 infection. Presenting first to the clinic with episodic dystonia and finger spasticity, the patient’s condition rapidly deteriorated with a significant drop in the Glasgow Coma Scale (GCS). Despite improvement following initial treatment with rituximab and intravenous immunoglobulin, the patient’s symptoms relapsed, and GCS further dropped to 3/15. Serial brain magnetic resonance imaging scans revealed diffuse parenchymal atrophy, ventricular enlargement, and spinal cord thickening. Autoimmune investigations were negative but clinical whole genome sequencing prioritized four gene variants, the most significant of which was a novel frameshift null variant of the X chromosomal TLR7 gene (c.1386_1389dup, p.[His464Ilefs*7]). This case illustrates a role for TLR7 in long-term COVID-19 complications and highlights that TLR7 deficiency in the future may be addressed as a therapeutic measure.https://www.frontiersin.org/articles/10.3389/fneur.2023.1268035/fullCOVID-19SARS-CoV-2TLR7hemizygousneurological deteriorationimmunodeficiency |
| spellingShingle | Ahmed Noor Eddin Mohammed Al-Rimawi Feham Peer-Zada Khalid Hundallah Amal Alhashem Amal Alhashem Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review Frontiers in Neurology COVID-19 SARS-CoV-2 TLR7 hemizygous neurological deterioration immunodeficiency |
| title | Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review |
| title_full | Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review |
| title_fullStr | Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review |
| title_full_unstemmed | Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review |
| title_short | Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review |
| title_sort | novel tlr7 hemizygous variant in post covid 19 neurological deterioration a case report with literature review |
| topic | COVID-19 SARS-CoV-2 TLR7 hemizygous neurological deterioration immunodeficiency |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1268035/full |
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