Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
28 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v8.39 | LGI1 |
Ida Ertmanska changed review comment from: As reviewed previously, monoallelic variants in LGI1 are associated with Autosomal Dominant Epilepsy with Auditory Features (ADEAF), also known as familial temporal lobe epilepsy. The LGI1-ADEAF association is Definitive in ClinGen, with penetrance estimated at 60% (https://search.clinicalgenome.org/CCID:005280). Individuals with monoallelic variants present with later-onset epilepsy and incomplete penetrance (e.g. PMID: 26773249 - cohort of 26 patients, average onset of epilepsy at 16.83 years). Recent evidence identifies cases with biallelic LGI1 variants, presenting with a more severe phenotype, including infantile lethality and severe intellectual disability: PMID: 40455867 Hirano et al., 2025 Report of 6 cases from 4 consanguineous unrelated families (Saudi Arabian, Pakistani, Jordanian, Turkish). All affected individuals presented with drug-resistant neonatal/infantile-onset seizures, as well as intellectual disability (mild in P4, severe ID in 5 other patients), delayed motor milestones. P2 died at age 9 months due to status epilepticus; P3 died of unknown cause at 4yo; patients 1A-C died of respiratory failure aged 11-24yo. Seq method: Trio WES (all), Sanger confirmation (with exception of P3). Variants: P1A-C: c.143G>T p.(Cys48Phe) – Revel 0.93, not in gnomAD v4 P2: c.931C>T p.(Arg311*) - not in gnomAD v4 P3: c.1570T>C p.(Ser524Pro) – Revel 0.67, 1 allele in gnomAD v4 (exome only) P4: c.1672T>G p.(Ter558GlyextTer23) – not in gnomAD v4 Additional functional evidence from PMID:40455867: Expressed wild-type LGI1 (WT) or newly identified LGI1 variants in HEK293T cells - secretion levels of LGI1 variants Cys48Phe and Ter558GlyextTer23 were somewhat reduced, while Arg311* and Ser524Pro levels were significantly reduced. Cell surface binding to ADAM22 in COS-7 cells (ADAM22 serves as a receptor for LGI1) - Arg311* and Ser524Pro did not show any binding, Cys48Phe and Ter558GlyextTer23 retained good binding activity. The functional impact of the variants on LGI1 function correlates well with the severity of clinical presentation. PMID: 41000458 Mouhi et al., 2025 Consanguineous Moroccan family, siblings with epileptic encephalopathy due to a homozygous variant within the LGI1 gene: c.245T>C (p.Ile82Thr) - Method: WES +Sanger; Revel = 0.97, not in gnomAD v4 Proband VI.1: seizures from birth, generalised clonic seizures, focal and generalised tonicoclonic seizures. Severe developmental delay at 4yo. Repeated EEG showed abnormal background activity. Younger brother (IV.2): seizures from the 1st week of life, died at the age of 11 months after repeated pulmonary infections. c.245T>C (p.Ile82Thr) also reported in a het state in PMID 24206907 – patient with autosomal dominant epilepsy with auditory aura. Paternal cousin heterozygous for the variant experienced moderate focal epilepsy; het parents unaffected. LGI1 is associated with AR Epilepsy, familial temporal lobe, 1 (600512) in OMIM - accessed 7th Oct 2025. Based on the recent evidence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.; to: As reviewed previously, monoallelic variants in LGI1 are associated with Autosomal Dominant Epilepsy with Auditory Features (ADEAF), also known as familial temporal lobe epilepsy. The LGI1-ADEAF association is Definitive in ClinGen, with penetrance estimated at 60% (https://search.clinicalgenome.org/CCID:005280). Individuals with monoallelic variants present with later-onset epilepsy and incomplete penetrance (e.g. PMID: 26773249 - cohort of 26 patients, average onset of epilepsy at 16.83 years). Recent evidence identifies cases with biallelic LGI1 variants, presenting with a more severe phenotype, including infantile lethality and severe intellectual disability: PMID: 40455867 Hirano et al., 2025 Report of 6 cases from 4 consanguineous unrelated families (Saudi Arabian, Pakistani, Jordanian, Turkish). All affected individuals presented with drug-resistant neonatal/infantile-onset seizures, as well as intellectual disability (mild in P4, severe ID in 5 other patients), delayed motor milestones. P2 died at age 9 months due to status epilepticus; P3 died of unknown cause at 4yo; patients 1A-C died of respiratory failure aged 11-24yo. Seq method: Trio WES (all), Sanger confirmation (with exception of P3). Variants: P1A-C: c.143G>T p.(Cys48Phe) – Revel 0.93, not in gnomAD v4 P2: c.931C>T p.(Arg311*) - not in gnomAD v4 P3: c.1570T>C p.(Ser524Pro) – Revel 0.67, 1 allele in gnomAD v4 (exome only) P4: c.1672T>G p.(Ter558GlyextTer23) – not in gnomAD v4 Additional functional evidence from PMID:40455867: Expressed wild-type LGI1 (WT) or newly identified LGI1 variants in HEK293T cells - secretion levels of LGI1 variants Cys48Phe and Ter558GlyextTer23 were somewhat reduced, while Arg311* and Ser524Pro levels were significantly reduced. Cell surface binding to ADAM22 in COS-7 cells (ADAM22 serves as a receptor for LGI1) - Arg311* and Ser524Pro did not show any binding, Cys48Phe and Ter558GlyextTer23 retained good binding activity. The functional impact of the variants on LGI1 function correlates well with the severity of clinical presentation. PMID: 41000458 Mouhi et al., 2025 Consanguineous Moroccan family, siblings with epileptic encephalopathy due to a homozygous variant within the LGI1 gene: c.245T>C (p.Ile82Thr) - Method: WES +Sanger; Revel = 0.97, not in gnomAD v4 Proband VI.1: seizures from birth, generalised clonic seizures, focal and generalised tonicoclonic seizures. Severe developmental delay at 4yo. Repeated EEG showed abnormal background activity. Younger brother (IV.2): seizures from the 1st week of life, died at the age of 11 months after repeated pulmonary infections. c.245T>C (p.Ile82Thr) also reported in a het state in PMID 24206907 – patient with autosomal dominant epilepsy with auditory aura. Paternal cousin heterozygous for the variant experienced moderate focal epilepsy; het parents unaffected. LGI1 is associated with AD Epilepsy, familial temporal lobe, 1 (600512) in OMIM - accessed 7th Oct 2025. Based on the recent evidence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v8.38 | LGI1 |
Ida Ertmanska changed review comment from: As reviewed previously, monoallelic variants in LGI1 are associated with Autosomal Dominant Epilepsy with Auditory Features (ADEAF), also known as familial temporal lobe epilepsy. The LGI1-ADEAF association is Definitive in ClinGen, with penetrance estimated at 60% (https://search.clinicalgenome.org/CCID:005280). Recent evidence identifies cases with biallelic LGI1 variants, presenting with a more severe phenotype, including infantile lethality and severe intellectual disability: PMID: 40455867 Hirano et al., 2025 Report of 6 cases from 4 consanguineous unrelated families (Saudi Arabian, Pakistani, Jordanian, Turkish). All affected individuals presented with drug-resistant neonatal/infantile-onset seizures, as well as intellectual disability (mild in P4, severe ID in 5 other patients), delayed motor milestones. P2 died at age 9 months due to status epilepticus; P3 died of unknown cause at 4yo; patients 1A-C died of respiratory failure aged 11-24yo. Seq method: Trio WES (all), Sanger confirmation (with exception of P3). Variants: P1A-C: c.143G>T p.(Cys48Phe) – Revel 0.93, not in gnomAD v4 P2: c.931C>T p.(Arg311*) - not in gnomAD v4 P3: c.1570T>C p.(Ser524Pro) – Revel 0.67, 1 allele in gnomAD v4 (exome only) P4: c.1672T>G p.(Ter558GlyextTer23) – not in gnomAD v4 Additional functional evidence from PMID:40455867: Expressed wild-type LGI1 (WT) or newly identified LGI1 variants in HEK293T cells - secretion levels of LGI1 variants Cys48Phe and Ter558GlyextTer23 were somewhat reduced, while Arg311* and Ser524Pro levels were significantly reduced. Cell surface binding to ADAM22 in COS-7 cells (ADAM22 serves as a receptor for LGI1) - Arg311* and Ser524Pro did not show any binding, Cys48Phe and Ter558GlyextTer23 retained good binding activity. The functional impact of the variants on LGI1 function correlates well with the severity of clinical presentation. PMID: 41000458 Mouhi et al., 2025 Consanguineous Moroccan family, siblings with epileptic encephalopathy due to a homozygous variant within the LGI1 gene: c.245T>C (p.Ile82Thr) - Method: WES +Sanger; Revel = 0.97, not in gnomAD v4 Proband VI.1: seizures from birth, generalised clonic seizures, focal and generalised tonicoclonic seizures. Severe developmental delay at 4yo. Repeated EEG showed abnormal background activity. Younger brother (IV.2): seizures from the 1st week of life, died at the age of 11 months after repeated pulmonary infections. c.245T>C (p.Ile82Thr) also reported in a het state in PMID 24206907 – patient with autosomal dominant epilepsy with auditory aura. Paternal cousin heterozygous for the variant experienced moderate focal epilepsy; het parents unaffected. LGI1 is associated with AR Epilepsy, familial temporal lobe, 1 (600512) in OMIM - accessed 7th Oct 2025. Based on the recent evidence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.; to: As reviewed previously, monoallelic variants in LGI1 are associated with Autosomal Dominant Epilepsy with Auditory Features (ADEAF), also known as familial temporal lobe epilepsy. The LGI1-ADEAF association is Definitive in ClinGen, with penetrance estimated at 60% (https://search.clinicalgenome.org/CCID:005280). Individuals with monoallelic variants present with later-onset epilepsy and incomplete penetrance (e.g. PMID: 26773249 - cohort of 26 patients, average onset of epilepsy at 16.83 years). Recent evidence identifies cases with biallelic LGI1 variants, presenting with a more severe phenotype, including infantile lethality and severe intellectual disability: PMID: 40455867 Hirano et al., 2025 Report of 6 cases from 4 consanguineous unrelated families (Saudi Arabian, Pakistani, Jordanian, Turkish). All affected individuals presented with drug-resistant neonatal/infantile-onset seizures, as well as intellectual disability (mild in P4, severe ID in 5 other patients), delayed motor milestones. P2 died at age 9 months due to status epilepticus; P3 died of unknown cause at 4yo; patients 1A-C died of respiratory failure aged 11-24yo. Seq method: Trio WES (all), Sanger confirmation (with exception of P3). Variants: P1A-C: c.143G>T p.(Cys48Phe) – Revel 0.93, not in gnomAD v4 P2: c.931C>T p.(Arg311*) - not in gnomAD v4 P3: c.1570T>C p.(Ser524Pro) – Revel 0.67, 1 allele in gnomAD v4 (exome only) P4: c.1672T>G p.(Ter558GlyextTer23) – not in gnomAD v4 Additional functional evidence from PMID:40455867: Expressed wild-type LGI1 (WT) or newly identified LGI1 variants in HEK293T cells - secretion levels of LGI1 variants Cys48Phe and Ter558GlyextTer23 were somewhat reduced, while Arg311* and Ser524Pro levels were significantly reduced. Cell surface binding to ADAM22 in COS-7 cells (ADAM22 serves as a receptor for LGI1) - Arg311* and Ser524Pro did not show any binding, Cys48Phe and Ter558GlyextTer23 retained good binding activity. The functional impact of the variants on LGI1 function correlates well with the severity of clinical presentation. PMID: 41000458 Mouhi et al., 2025 Consanguineous Moroccan family, siblings with epileptic encephalopathy due to a homozygous variant within the LGI1 gene: c.245T>C (p.Ile82Thr) - Method: WES +Sanger; Revel = 0.97, not in gnomAD v4 Proband VI.1: seizures from birth, generalised clonic seizures, focal and generalised tonicoclonic seizures. Severe developmental delay at 4yo. Repeated EEG showed abnormal background activity. Younger brother (IV.2): seizures from the 1st week of life, died at the age of 11 months after repeated pulmonary infections. c.245T>C (p.Ile82Thr) also reported in a het state in PMID 24206907 – patient with autosomal dominant epilepsy with auditory aura. Paternal cousin heterozygous for the variant experienced moderate focal epilepsy; het parents unaffected. LGI1 is associated with AR Epilepsy, familial temporal lobe, 1 (600512) in OMIM - accessed 7th Oct 2025. Based on the recent evidence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v8.38 | LGI1 |
Ida Ertmanska changed review comment from: As reviewed previously, monoallelic variants in LGI1 are associated with Autosomal Dominant Epilepsy with Auditory Features (ADEAF), also known as familial temporal lobe epilepsy. The LGI1-ADEAF association is Definitive in ClinGen, with penetrance estimated at 60% (https://search.clinicalgenome.org/CCID:005280). Recent evidence identifies cases with biallelic LGI1 variants, presenting with a more severe phenotype, including infantile lethality and severe intellectual disability: PMID: 40455867 Hirano et al., 2025 Report of 6 cases from 4 consanguineous unrelated families (Saudi Arabian, Pakistani, Jordanian, Turkish). All affected individuals presented with drug-resistant neonatal/infantile-onset seizures, as well as intellectual disability (mild in P4, severe ID in 5 other patients), delayed motor milestones. P2 died at age 9 months due to status epilepticus; P3 died of unknown cause at 4yo; patients 1A-C died of respiratory failure aged 11-24yo. Seq method: Trio WES (all), Sanger confirmation (with exception of P3). Variants: P1A-C: c.143G>T p.(Cys48Phe) – Revel 0.93, not in gnomAD v4 P2: c.931C>T p.(Arg311*) - not in gnomAD v4 P3: c.1570T>C p.(Ser524Pro) – Revel 0.67, 1 allele in gnomAD v4 (exome only) P4: c.1672T>G p.(Ter558GlyextTer23) – not in gnomAD v4 PMID: 41000458 Mouhi et al., 2025 Consanguineous Moroccan family, siblings with epileptic encephalopathy due to a homozygous variant within the LGI1 gene: c.245T>C (p.Ile82Thr) - Method: WES +Sanger; Revel = 0.97, not in gnomAD v4 Proband VI.1: seizures from birth, generalised clonic seizures, focal and generalised tonicoclonic seizures. Severe developmental delay at 4yo. Repeated EEG showed abnormal background activity. Younger brother (IV.2): seizures from the 1st week of life, died at the age of 11 months after repeated pulmonary infections. c.245T>C (p.Ile82Thr) also reported in a het state in PMID 24206907 – patient with autosomal dominant epilepsy with auditory aura. Paternal cousin heterozygous for the variant experienced moderate focal epilepsy; het parents unaffected (variable penetrance, estimated at 60% by ClinGen). LGI1 is associated with AR Epilepsy, familial temporal lobe, 1 (600512) in OMIM - accessed 7th Oct 2025. Based on the recent evidence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.; to: As reviewed previously, monoallelic variants in LGI1 are associated with Autosomal Dominant Epilepsy with Auditory Features (ADEAF), also known as familial temporal lobe epilepsy. The LGI1-ADEAF association is Definitive in ClinGen, with penetrance estimated at 60% (https://search.clinicalgenome.org/CCID:005280). Recent evidence identifies cases with biallelic LGI1 variants, presenting with a more severe phenotype, including infantile lethality and severe intellectual disability: PMID: 40455867 Hirano et al., 2025 Report of 6 cases from 4 consanguineous unrelated families (Saudi Arabian, Pakistani, Jordanian, Turkish). All affected individuals presented with drug-resistant neonatal/infantile-onset seizures, as well as intellectual disability (mild in P4, severe ID in 5 other patients), delayed motor milestones. P2 died at age 9 months due to status epilepticus; P3 died of unknown cause at 4yo; patients 1A-C died of respiratory failure aged 11-24yo. Seq method: Trio WES (all), Sanger confirmation (with exception of P3). Variants: P1A-C: c.143G>T p.(Cys48Phe) – Revel 0.93, not in gnomAD v4 P2: c.931C>T p.(Arg311*) - not in gnomAD v4 P3: c.1570T>C p.(Ser524Pro) – Revel 0.67, 1 allele in gnomAD v4 (exome only) P4: c.1672T>G p.(Ter558GlyextTer23) – not in gnomAD v4 Additional functional evidence from PMID:40455867: Expressed wild-type LGI1 (WT) or newly identified LGI1 variants in HEK293T cells - secretion levels of LGI1 variants Cys48Phe and Ter558GlyextTer23 were somewhat reduced, while Arg311* and Ser524Pro levels were significantly reduced. Cell surface binding to ADAM22 in COS-7 cells (ADAM22 serves as a receptor for LGI1) - Arg311* and Ser524Pro did not show any binding, Cys48Phe and Ter558GlyextTer23 retained good binding activity. The functional impact of the variants on LGI1 function correlates well with the severity of clinical presentation. PMID: 41000458 Mouhi et al., 2025 Consanguineous Moroccan family, siblings with epileptic encephalopathy due to a homozygous variant within the LGI1 gene: c.245T>C (p.Ile82Thr) - Method: WES +Sanger; Revel = 0.97, not in gnomAD v4 Proband VI.1: seizures from birth, generalised clonic seizures, focal and generalised tonicoclonic seizures. Severe developmental delay at 4yo. Repeated EEG showed abnormal background activity. Younger brother (IV.2): seizures from the 1st week of life, died at the age of 11 months after repeated pulmonary infections. c.245T>C (p.Ile82Thr) also reported in a het state in PMID 24206907 – patient with autosomal dominant epilepsy with auditory aura. Paternal cousin heterozygous for the variant experienced moderate focal epilepsy; het parents unaffected. LGI1 is associated with AR Epilepsy, familial temporal lobe, 1 (600512) in OMIM - accessed 7th Oct 2025. Based on the recent evidence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.491 | ADAM22 | Sarah Leigh Tag for-review was removed from gene: ADAM22. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.491 | ADAM22 | Sarah Leigh commented on gene: ADAM22: NHSGenomic Medicine Service consideration - the amber rating is appropriate for this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.491 | ADAM22 | Sarah Leigh commented on gene: ADAM22: After NHSGenomic Medicine Service consideration, the rating of this gene has not been changed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.295 | ADAM22 | Sarah Leigh changed review comment from: Comment on list classification: There is just enough evidence for this gene to be rated GREEN at the next major review, which may make it a boarderline case.; to: Comment on list classification: There is just enough evidence for this gene to be rated GREEN at the next major review, which may make it a borderline case. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.295 | ADAM22 | Sarah Leigh Classified gene: ADAM22 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.295 | ADAM22 | Sarah Leigh Added comment: Comment on list classification: There is just enough evidence for this gene to be rated GREEN at the next major review, which may make it a boarderline case. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.295 | ADAM22 | Sarah Leigh Gene: adam22 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.288 | ADAM22 | Sarah Leigh Tag for-review tag was added to gene: ADAM22. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.288 | ADAM22 | Sarah Leigh reviewed gene: ADAM22: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.288 | ADAM22 | Sarah Leigh Phenotypes for gene: ADAM22 were changed from ?Epileptic encephalopathy, early infantile, 61 OMIM:617933 to ?Epileptic encephalopathy, early infantile, 61 OMIM:617933; developmental and epileptic encephalopathy, 61 MONDO:0033370 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.287 | ADAM22 | Sarah Leigh Tag watchlist tag was added to gene: ADAM22. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.280 | ADAM22 | Sarah Leigh Phenotypes for gene: ADAM22 were changed from ?Epileptic encephalopathy, early infantile, 61, 617933 to ?Epileptic encephalopathy, early infantile, 61 OMIM:617933 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.277 | ADAM22 | Sarah Leigh Publications for gene: ADAM22 were set to 27066583; 30237576; 15876356 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.274 | ADAM22 | Helen Lord reviewed gene: ADAM22: Rating: AMBER; Mode of pathogenicity: None; Publications: 31432233, 33397806; Phenotypes: Developmental and epileptic encephalopathy 61; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.47 | ADAM22 | Rebecca Foulger changed review comment from: Comment on list classification: 2 Families with prominent seizure phenotype and biallelic ADAM22 variants reported (PMIDs:30237576, 27066583). Plus mouse model of seizures. Not yet associated with a disorder in Gene2Phenotype. Amber is appropriate rating awaiting further cases.; to: Comment on list classification: Added to panel and rated Amber by Zornitza Stark. 2 families with prominent seizure phenotype and biallelic ADAM22 variants reported (PMIDs:30237576, 27066583). Plus mouse model of seizures. Not yet associated with a disorder in Gene2Phenotype. Amber is appropriate rating awaiting further cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.47 | ADAM22 | Rebecca Foulger Classified gene: ADAM22 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.47 | ADAM22 | Rebecca Foulger Added comment: Comment on list classification: 2 Families with prominent seizure phenotype and biallelic ADAM22 variants reported (PMIDs:30237576, 27066583). Plus mouse model of seizures. Not yet associated with a disorder in Gene2Phenotype. Amber is appropriate rating awaiting further cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.47 | ADAM22 | Rebecca Foulger Gene: adam22 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.46 | ADAM22 | Rebecca Foulger Publications for gene: ADAM22 were set to 27066583; 30237576 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.45 | ADAM22 | Rebecca Foulger commented on gene: ADAM22: Mouse model: Adam22-/- mice develop lethal seizures during the first postnatal weeks (e.g. PMID:15876356). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.45 | ADAM22 | Rebecca Foulger Phenotypes for gene: ADAM22 were changed from Epileptic encephalopathy, early infantile, 61, 617933 to ?Epileptic encephalopathy, early infantile, 61, 617933 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.44 | ADAM22 | Rebecca Foulger commented on gene: ADAM22: PMID:30237576 (Maddirevula et al., 2019) searched their database of clinical exomes for homozygous variants and report an 18 year old male with an Arg860* variant in ADAM22. Seizures started age 5 months with a focal seizure, and continued with generalized tonic clonic seizures and status epilepticus (Supplementary Table). His development was normal until 5 months when he had a slower gain of milestones. He has ID with severely delayed speech. Family history revealed ID and epilepsy in his old brother and in wider family. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.44 | ADAM22 | Rebecca Foulger commented on gene: ADAM22 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.44 | ADAM22 | Rebecca Foulger Phenotypes for gene: ADAM22 were changed from Epileptic encephalopathy, early infantile, 61, MIM# 617933 to Epileptic encephalopathy, early infantile, 61, 617933 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.0 | ADAM22 |
Zornitza Stark gene: ADAM22 was added gene: ADAM22 was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAM22 were set to 27066583; 30237576 Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933 Review for gene: ADAM22 was set to AMBER Added comment: Two families reported; the second one as part of a large consanguineous cohort. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||