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| Mendeliome v1.2799 | AMFR | Zornitza Stark Phenotypes for gene: AMFR were changed from Spastic paraplegia 89, autosomal recessive, MIM# 620379 to Spastic paraplegia 89, autosomal recessive, MIM# 620379; Inborn error of immunity, MONDO:0003778, AMFR-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2798 | AMFR | Zornitza Stark Publications for gene: AMFR were set to 37119330 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2797 | AMFR |
Zornitza Stark edited their review of gene: AMFR: Added comment: PMID 38277122: Single case report of 3-year-old boy in whom varicella followed a complicated course with thrombocytopenia, haemorrhagic and necrotic lesions, pneumonitis, and intermittent encephalopathy. HLH was the working diagnosis. Although the clinical condition improved, longstanding hemophagocytosis followed despite therapy. Rare monoallelic variant in autocrine motility factor receptor (AMFR) identified. AMFR encodes a ubiquitin ligase involved in innate cytosolic DNA sensing and interferon (IFN) production through the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway. Peripheral blood mononuclear cells (PBMCs) from the patient exhibited impaired signaling downstream of STING in response dsDNA and 2'3'-cGAMP, agonists of cGAS and STING, respectively, and fibroblasts from the patient showed impaired type I IFN responses and significantly increased VZV replication. Overexpression of the variant AMFR R594C resulted in decreased K27-linked STING ubiquitination compared to WT AMFR. Moreover, ImageStream technology revealed reduced STING trafficking from ER to Golgi in cells expressing the patient AMFR R594C variant. This was supported by a dose-dependent dominant negative effect of expression of the patient AMFR variant as measured by IFN-β reporter gene assay. Finally, lentiviral transduction with WT AMFR partially reconstituted 2'3'-cGAMP-induced STING-mediated signaling and ISG expression in patient PBMCs. This work links defective AMFR-STING signaling to severe VZV disease and hyperinflammation and suggests a direct role for cGAS-STING in the control of viral infections in humans. RED for this association.; Changed publications: 38277122; Changed phenotypes: Spastic paraplegia 89, autosomal recessive, MIM# 620379, Inborn error of immunity, MONDO:0003778, AMFR-related |
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| Mendeliome v1.894 | AMFR | Zornitza Stark Marked gene: AMFR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.894 | AMFR | Zornitza Stark Gene: amfr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.894 | AMFR | Zornitza Stark Phenotypes for gene: AMFR were changed from Hereditary spastic paraplegia, MONDO:0019064 to Spastic paraplegia 89, autosomal recessive, MIM# 620379 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.893 | AMFR | Zornitza Stark Classified gene: AMFR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.893 | AMFR | Zornitza Stark Gene: amfr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.892 | AMFR | Zornitza Stark reviewed gene: AMFR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 89, autosomal recessive, MIM# 620379; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.869 | AMFR |
Yetong Chen gene: AMFR was added gene: AMFR was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AMFR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AMFR were set to 37119330 Phenotypes for gene: AMFR were set to Hereditary spastic paraplegia, MONDO:0019064 Review for gene: AMFR was set to GREEN Added comment: PMID 37119330 reports 20 individuals harbouring AMFR variants from 8 unrelated, consanguineous families. All patients had early disease onset (<3 years), including motor delay, lower limb hyperreflexia and spastic paraplegia that match the typical phenotypes of hereditary spastic paraplegia. Sources: Literature |
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