Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
21 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v8.74 | RANBP2 |
Ida Ertmanska changed review comment from: RANBP2 is predicted to be dosage sensitive (pLI score = 1.00) - https://www.deciphergenomics.org/gene/RANBP2/overview/clinical-info. This gene is putatively linked to AD Encephalopathy, acute, infection-induced, 3, susceptibility to - MIM:608033 (OMIM accessed 21st Nov 2025). PMID: 40538544 Varghese et al., 2025 Case 1 - previously healthy 23-month-old female presented with lethargy and acute-onset encephalopathy, following a 2-day fever. Brain MRI consistent with Acute necrotizing encephalopathy (ANE). She presented with another episode of acute-onset encephalopathy at 4yrs 10 mo; she remains non-verbal and non-ambulatory. Family history: 2 maternal uncles, deceased at 16 & 22 months old - both with working diagnoses of Leigh-like disease. Patient was heterozygous for c.1754C>G, p.Thr585Met (maternally inherited) - rare in gnomAD v4.1.0 (2 heterozygotes), Revel score = 0.18 Benign Moderate. Seq method: rapid Trio WES. Case 2 - A 24-month-old male, previously described in PMID: 36632547 Olubiyi et al., 2022. Patient presented with acute encephalopathy, seizures, and emesis. Positive for respiratory SARS-CoV-2; brain MRI concerning for ANE; discharged from hospital on day 7. Presented again at 30 months with acute-onset encephalopathy, delirium, and seizures. At 4.5yrs, patient is much improved - he was forming sentences and ambulated independently with a mildly ataxic gait, WPPSI-IV IQ 65 (mild ID). Heterozygous for RANBP2 c.1966A>G (p.Ile656Val) - maternally inherited; variant rare in gnomAD v4.1.0 (1 heterozygote), Revel score = 0.31 Uncertain. PMID: 38050538 Li et al., 2023 Report of 1‐year‐old girl - presented with influenza‐associated encephalopathy after which she made a full recovery; followed by severe acute respiratory syndrome coronavirus 2 infection - the patient presented with seizures and deteriorating mental status. Brain MRI revealed necrotic lesions. WES revealed heterozygous c.1754C>T, p.Thr585Met and c.6952G>A, p.Asp2318Asn variants in RANBP2 (presumed in cis?). Variant c.6952G>A, p.Asp2318Asn is not in gnomAD v4, Revel score = 0.34 Benign Supporting. The penetrance of RANBP2 missense variants is estimated at around 40%. PMID: 36621064 Forest et al., 2023 Report of a 10-year-old girl with acute onset of decreased level of consciousness and fever. Brain and spinal cord MRI confirmed extensive areas of cytotoxic edema; MRI suggestive for necrosis. Diagnosed with ANE associated with Sars-CoV-2 infection. First episode noted to be at 2yo - trigerred by Influenza A. WES revealed a de novo c.1754C>T p.(Thr585Met) mutation in RANBP2. PMID: 34377735 Hartley et al., 2021 Case 1 - 9 month old female presented with a seizure, following 4 days of fever; developed weakness and spasticity in her left side, and developmental regression; positive for Human herpesvirus 6. Seizures recurred 2 years later. Gene panel test detected a heterozygous mutation in RANBP2 (c.1754C>T; p.Thr585Met) - parents not genotyped. Case 2 - 6-year-old female with no significant past medical history; presented in cardiac arrest likely secondary to hypoxia from refractory status epilepticus; frequent seizures, EEG abnormal, brain MRI was positive for symmetric T2 lesions. Patient recovered after 42 days. Gene panel showed patient was heterozygous for a c.1350A>T; p.Leu450Phe variant in RANBP2 - maternally inherited, 6 heterozygotes reported in gnomAD v4.1.0., Revel score = 0.06 Benign Moderate.; to: PMID: 40538544 Varghese et al., 2025 Case 1 - previously healthy 23-month-old female presented with lethargy and acute-onset encephalopathy, following a 2-day fever. Brain MRI consistent with Acute necrotizing encephalopathy (ANE). She presented with another episode of acute-onset encephalopathy at 4yrs 10 mo; she remains non-verbal and non-ambulatory. Family history: 2 maternal uncles, deceased at 16 & 22 months old - both with working diagnoses of Leigh-like disease. Patient was heterozygous for c.1754C>G, p.Thr585Met (maternally inherited) - rare in gnomAD v4.1.0 (2 heterozygotes), Revel score = 0.18 Benign Moderate. Seq method: rapid Trio WES. Case 2 - A 24-month-old male, previously described in PMID: 36632547 Olubiyi et al., 2022. Patient presented with acute encephalopathy, seizures, and emesis. Positive for respiratory SARS-CoV-2; brain MRI concerning for ANE; discharged from hospital on day 7. Presented again at 30 months with acute-onset encephalopathy, delirium, and seizures. At 4.5yrs, patient is much improved - he was forming sentences and ambulated independently with a mildly ataxic gait, WPPSI-IV IQ 65 (mild ID). Heterozygous for RANBP2 c.1966A>G (p.Ile656Val) - maternally inherited; variant rare in gnomAD v4.1.0 (1 heterozygote), Revel score = 0.31 Uncertain. PMID: 38050538 Li et al., 2023 Report of 1‐year‐old girl - presented with influenza‐associated encephalopathy after which she made a full recovery; followed by severe acute respiratory syndrome coronavirus 2 infection - the patient presented with seizures and deteriorating mental status. Brain MRI revealed necrotic lesions. WES revealed heterozygous c.1754C>T, p.Thr585Met and c.6952G>A, p.Asp2318Asn variants in RANBP2 (presumed in cis?). Variant c.6952G>A, p.Asp2318Asn is not in gnomAD v4, Revel score = 0.34 Benign Supporting. The penetrance of RANBP2 missense variants is estimated at around 40%. PMID: 36621064 Forest et al., 2023 Report of a 10-year-old girl with acute onset of decreased level of consciousness and fever. Brain and spinal cord MRI confirmed extensive areas of cytotoxic edema; MRI suggestive for necrosis. Diagnosed with ANE associated with Sars-CoV-2 infection. First episode noted to be at 2yo - trigerred by Influenza A. WES revealed a de novo c.1754C>T p.(Thr585Met) mutation in RANBP2. PMID: 34377735 Hartley et al., 2021 Case 1 - 9 month old female presented with a seizure, following 4 days of fever; developed weakness and spasticity in her left side, and developmental regression; positive for Human herpesvirus 6. Seizures recurred 2 years later. Gene panel test detected a heterozygous mutation in RANBP2 (c.1754C>T; p.Thr585Met) - parents not genotyped. Case 2 - 6-year-old female with no significant past medical history; presented in cardiac arrest likely secondary to hypoxia from refractory status epilepticus; frequent seizures, EEG abnormal, brain MRI was positive for symmetric T2 lesions. Patient recovered after 42 days. Gene panel showed patient was heterozygous for a c.1350A>T; p.Leu450Phe variant in RANBP2 - maternally inherited, 6 heterozygotes reported in gnomAD v4.1.0., Revel score = 0.06 Benign Moderate. RANBP2 is predicted to be dosage sensitive (pLI score = 1.00) - https://www.deciphergenomics.org/gene/RANBP2/overview/clinical-info. This gene is putatively linked to AD Encephalopathy, acute, infection-induced, 3, susceptibility to - MIM:608033 (OMIM accessed 21st Nov 2025). RANBP2 association with familial acute necrotizing encephalopathy has been classified as Moderate in ClinGen by the Epilepsy Expert panel (April 2024) and Limited for Leigh Syndrome (Mitochondrial Diseases Expert Panel, June 2021). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v8.74 | RANBP2 |
Ida Ertmanska changed review comment from: RANBP2 is predicted to be dosage sensitive (pLI score = 1.00) - https://www.deciphergenomics.org/gene/RANBP2/overview/clinical-info. This gene is putatively linked to AD Encephalopathy, acute, infection-induced, 3, susceptibility to - MIM:608033 (OMIM accessed 21st Nov 2025). PMID: 40538544 Varghese et al., 2025 Case 1 - previously healthy 23-month-old female presented with lethargy and acute-onset encephalopathy, following a 2-day fever. Brain MRI consistent with Acute necrotizing encephalopathy (ANE). She presented with another episode of acute-onset encephalopathy at 4yrs 10 mo; she remains non-verbal and non-ambulatory. Family history: 2 maternal uncles, deceased at 16 & 22 months old - both with working diagnoses of Leigh-like disease. Patient was heterozygous for c.1754C>G, p.Thr585Met (maternally inherited) - rare in gnomAD v4.1.0 (2 heterozygotes), Revel score = 0.18 Benign Moderate. Seq method: rapid Trio WES. Case 2 - A 24-month-old male, previously described in PMID: 36632547 Olubiyi et al., 2022. Patient presented with acute encephalopathy, seizures, and emesis. Positive for respiratory SARS-CoV-2; brain MRI concerning for ANE; discharged from hospital on day 7. Presented again at 30 months with acute-onset encephalopathy, delirium, and seizures. At 4.5yrs, patient is much improved - he was forming sentences and ambulated independently with a mildly ataxic gait, WPPSI-IV IQ 65 (mild ID). Heterozygous for RANBP2 c.1966A>G (p.Ile656Val) - maternally inherited; variant rare in gnomAD v4.1.0 (1 heterozygote), Revel score = 0.31 Uncertain. PMID: 38050538 Li et al., 2023 Report of 1‐year‐old girl - presented with influenza‐associated encephalopathy after which she made a full recovery; followed by severe acute respiratory syndrome coronavirus 2 infection - the patient presented with seizures and deteriorating mental status. Brain MRI revealed necrotic lesions. WES revealed heterozygous c.1754C>T, p.Thr585Met and c.6952G>A, p.Asp2318Asn variants in RANBP2 (presumed in cis?). Variant c.6952G>A, p.Asp2318Asn is not in gnomAD v4, Revel score = 0.34 Benign Supporting. The penetrance of RANBP2 missense variants is estimated at around 40%. PMID: 36621064 Forest et al., 2023 Report of a 10-year-old girl with acute onset of decreased level of consciousness and fever. Brain and spinal cord MRI confirmed extensive areas of cytotoxic edema; MRI suggestive for necrosis. Diagnosed with ANE associated with Sars-CoV-2 infection. First episode noted to be at 2yo - trigerred by Influenza A. WES revealed a de novo c.1754C>T p.(Thr585Met) mutation in RANBP2. PMID: 34377735 Hartley et al., 2021 Case 1 - 9 month old female presented with a seizure, following 4 days of fever; developed weakness and spasticity in her left side, and developmental regression; positive for Human herpesvirus 6. Seizures recurred 2 years later. Gene panel test detected a heterozygous mutation in RANBP2 (c.1754C>T; p.Thr585Met) - parents not genotyped. Case 2 - 6-year-old female with no significant past medical history; presented in cardiac arrest likely secondary to hypoxia from refractory status epilepticus; frequent seizures, EEG abnormal, brain MRI was positive for symmetric T2 lesions. Gene panel showed patient was heterozygous for a c.1350A>T; p.Leu450Phe variant in RANBP2 - maternally inherited, 6 heterozygotes reported in gnomAD v4.1.0., Revel score = 0.06 Benign Moderate. PMID: 32426208 Levine et al., 2020; to: RANBP2 is predicted to be dosage sensitive (pLI score = 1.00) - https://www.deciphergenomics.org/gene/RANBP2/overview/clinical-info. This gene is putatively linked to AD Encephalopathy, acute, infection-induced, 3, susceptibility to - MIM:608033 (OMIM accessed 21st Nov 2025). PMID: 40538544 Varghese et al., 2025 Case 1 - previously healthy 23-month-old female presented with lethargy and acute-onset encephalopathy, following a 2-day fever. Brain MRI consistent with Acute necrotizing encephalopathy (ANE). She presented with another episode of acute-onset encephalopathy at 4yrs 10 mo; she remains non-verbal and non-ambulatory. Family history: 2 maternal uncles, deceased at 16 & 22 months old - both with working diagnoses of Leigh-like disease. Patient was heterozygous for c.1754C>G, p.Thr585Met (maternally inherited) - rare in gnomAD v4.1.0 (2 heterozygotes), Revel score = 0.18 Benign Moderate. Seq method: rapid Trio WES. Case 2 - A 24-month-old male, previously described in PMID: 36632547 Olubiyi et al., 2022. Patient presented with acute encephalopathy, seizures, and emesis. Positive for respiratory SARS-CoV-2; brain MRI concerning for ANE; discharged from hospital on day 7. Presented again at 30 months with acute-onset encephalopathy, delirium, and seizures. At 4.5yrs, patient is much improved - he was forming sentences and ambulated independently with a mildly ataxic gait, WPPSI-IV IQ 65 (mild ID). Heterozygous for RANBP2 c.1966A>G (p.Ile656Val) - maternally inherited; variant rare in gnomAD v4.1.0 (1 heterozygote), Revel score = 0.31 Uncertain. PMID: 38050538 Li et al., 2023 Report of 1‐year‐old girl - presented with influenza‐associated encephalopathy after which she made a full recovery; followed by severe acute respiratory syndrome coronavirus 2 infection - the patient presented with seizures and deteriorating mental status. Brain MRI revealed necrotic lesions. WES revealed heterozygous c.1754C>T, p.Thr585Met and c.6952G>A, p.Asp2318Asn variants in RANBP2 (presumed in cis?). Variant c.6952G>A, p.Asp2318Asn is not in gnomAD v4, Revel score = 0.34 Benign Supporting. The penetrance of RANBP2 missense variants is estimated at around 40%. PMID: 36621064 Forest et al., 2023 Report of a 10-year-old girl with acute onset of decreased level of consciousness and fever. Brain and spinal cord MRI confirmed extensive areas of cytotoxic edema; MRI suggestive for necrosis. Diagnosed with ANE associated with Sars-CoV-2 infection. First episode noted to be at 2yo - trigerred by Influenza A. WES revealed a de novo c.1754C>T p.(Thr585Met) mutation in RANBP2. PMID: 34377735 Hartley et al., 2021 Case 1 - 9 month old female presented with a seizure, following 4 days of fever; developed weakness and spasticity in her left side, and developmental regression; positive for Human herpesvirus 6. Seizures recurred 2 years later. Gene panel test detected a heterozygous mutation in RANBP2 (c.1754C>T; p.Thr585Met) - parents not genotyped. Case 2 - 6-year-old female with no significant past medical history; presented in cardiac arrest likely secondary to hypoxia from refractory status epilepticus; frequent seizures, EEG abnormal, brain MRI was positive for symmetric T2 lesions. Patient recovered after 42 days. Gene panel showed patient was heterozygous for a c.1350A>T; p.Leu450Phe variant in RANBP2 - maternally inherited, 6 heterozygotes reported in gnomAD v4.1.0., Revel score = 0.06 Benign Moderate. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.114 | SARS | Arina Puzriakova Tag Q1_23_promote_green was removed from gene: SARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.110 | SARS | Arina Puzriakova commented on gene: SARS: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.109 | SARS |
Arina Puzriakova Source NHS GMS was added to SARS. Source Expert Review Green was added to SARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.101 | SARS | Arina Puzriakova Publications for gene: SARS were set to 28236339; 34570399; 35790048 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.100 | SARS | Arina Puzriakova edited their review of gene: SARS: Changed publications to: 35790048, 36041817 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.100 | SARS |
Arina Puzriakova changed review comment from: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified. Single patient identified with de novo heterozygous splice site deletion (c.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect.; to: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified. PMID: 36041817 - Single patient identified with de novo heterozygous splice site deletion (c.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.100 | SARS |
Arina Puzriakova changed review comment from: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified. Single patient identified with de novo heterozygous splice site deletion (.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect.; to: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified. Single patient identified with de novo heterozygous splice site deletion (c.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.100 | SARS |
Arina Puzriakova Added comment: Comment on mode of inheritance: As only a single dominant case has been reported (details below), leaving MOI as biallelic for now with a watchlist_moi tag. Consider adding to other relevant panels if further cases are identified. Single patient identified with de novo heterozygous splice site deletion (.969_969+2delGGT) in the SARS1 gene. Phenotypes included complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Functional studies in both yeast strains and patient fibroblasts demonstrated a LoF, dominant negative effect. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.100 | SARS | Arina Puzriakova Mode of inheritance for gene: SARS was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.99 | SARS | Arina Puzriakova Tag watchlist_moi tag was added to gene: SARS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.99 | SARS | Arina Puzriakova Phenotypes for gene: SARS were changed from ?Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709 to Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.98 | SARS | Arina Puzriakova Publications for gene: SARS were set to 28236339; 34570399 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.97 | SARS | Arina Puzriakova Classified gene: SARS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.97 | SARS | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated cases with biallelic variants in this gene - seizures detected in all families. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.97 | SARS | Arina Puzriakova Gene: sars has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.96 | SARS |
Arina Puzriakova Tag watchlist was removed from gene: SARS. Tag Q1_23_promote_green tag was added to gene: SARS. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v3.96 | SARS | Arina Puzriakova reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.446 | SARS | Ivone Leong Entity copied from Intellectual disability v3.1356 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.446 | SARS |
Ivone Leong gene: SARS was added gene: SARS was added to Genetic epilepsy syndromes. Sources: Expert Review Amber,Literature watchlist, new-gene-name tags were added to gene: SARS. Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SARS were set to 28236339; 34570399 Phenotypes for gene: SARS were set to ?Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||