Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
17 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.4 | UNC13A | Achchuthan Shanmugasundram Tag Q4_25_NHS_review tag was added to gene: UNC13A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.4 | UNC13A | Ida Ertmanska Phenotypes for gene: UNC13A were changed from to congenital myasthenic syndrome, MONDO:0018940 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.3 | UNC13A | Ida Ertmanska Publications for gene: UNC13A were set to 27648472 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.2 | UNC13A | Ida Ertmanska Classified gene: UNC13A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.2 | UNC13A | Ida Ertmanska Gene: unc13a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.1 | UNC13A | Ida Ertmanska Tag Q4_25_promote_green tag was added to gene: UNC13A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.1 | UNC13A | Ida Ertmanska commented on gene: UNC13A: Comment on list classification: There are 2 unrelated individuals with biallelic putative LoF variants in UNC13A who presented with congenital hypotonia and sever muscle weakness. Additionally, knockout mouse models show that Unc13A deficiency interferes with the synaptic maturation process. In contrast, 4 unrelated individuals with heterozygous missense variants in UNC13A presented with intellectual disability and seizures. Hence, there are two distinct disease entities, with different MOIs, associated with this gene. Based on the available evidence, UNC13A should be promoted to Green for Congenital myaesthenic syndrome at the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.1 | UNC13A |
Ida Ertmanska changed review comment from: BIALLELIC CASES: PMID: 27648472 Engel et al., 2016 Report of a native American girl, born prematurely at 32 weeks - hypotonic at birth, needed ventilatory support, developed aspiration pneumonia; died at age 50 months due to respiratory failure; EMG studies revealed abnormally low-amplitude CMAPs at rest; histochemical studies of the anconeus muscle revealed marked type 2 fiber atrophy and type 1 fiber hypertrophy; homozygous for NM_001080421.2; c.304C>T, p.(Gln102*) in UNC13A - variant extremely rare in gnomAD v4.1.0., no homozygotes; method: WES. PMID: 36447687 Mullins et al., 2022 Case report of a female infant with congenital encephalopathy and a severe neuromuscular phenotype - delivered at 40 weeks due to abnormal heart rate and reduced fetal movement; she had mildly dysmorphic features, alternating hypertonia and hypotonia, extreme generalized muscle weakness, severe kyphoscoliosis and hernias. She died at 8 months due to bronchopneumonia. Homozygous for c.1188delC p.(Asp397Thrfs*107) in UNC13A - variant extremely rare in gnomAD v4.1.0., no homozygotes; method: WES. MONOALLELIC: 4 heterozygous cases harbouring missense variants in UNC13A have been detailed previously by Tom Hodgkinson (see below) - individuals presented with seizures and intellectual disability, NOT myaesthenic syndrome. This gene is not yet associated with a phenotype in OMIM (accessed 12th Nov 2025).; to: BIALLELIC CASES: PMID: 27648472 Engel et al., 2016 Report of a native American girl, born prematurely at 32 weeks - hypotonic at birth, needed ventilatory support, developed aspiration pneumonia; died at age 50 months due to respiratory failure; EMG studies revealed abnormally low-amplitude CMAPs at rest; histochemical studies of the anconeus muscle revealed marked type 2 fiber atrophy and type 1 fiber hypertrophy; homozygous for NM_001080421.2; c.304C>T, p.(Gln102*) in UNC13A - variant extremely rare in gnomAD v4.1.0., no homozygotes; method: WES. PMID: 36447687 Mullins et al., 2022 Case report of a female infant with congenital encephalopathy and a severe neuromuscular phenotype - delivered at 40 weeks due to abnormal heart rate and reduced fetal movement; she had mildly dysmorphic features, alternating hypertonia and hypotonia, extreme generalized muscle weakness, severe kyphoscoliosis and hernias. She died at 8 months due to bronchopneumonia. Homozygous for c.1188delC p.(Asp397Thrfs*107) in UNC13A - variant extremely rare in gnomAD v4.1.0., no homozygotes; method: WES. MONOALLELIC: 4 heterozygous cases harbouring missense variants in UNC13A have been detailed previously by Tom Hodgkinson (see below) - individuals presented with seizures and intellectual disability, NOT myaesthenic syndrome. FUNCTIONAL EVIDENCE: PMID: 10440375 Augustin et al., 1999: In glutamatergic hippocampal neurons from Unc13A -/- mice the synaptic-vesicle cycle is arrested at the maturation step, stopping transmitter release from the synapses. PMID: 15988013 Frédérique Varoqueaux et al., 2005: Triple knockout of Unc13A/B/C in the mouse results in paralysis and death; double knockout Unc13B/C mice were viable and fertile - thus, Unc13A was highlighted as crucial for CNS development and function. This gene is not yet associated with a phenotype in OMIM (accessed 12th Nov 2025). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.1 | UNC13A | Ida Ertmanska reviewed gene: UNC13A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27648472, 28192369, 39634123; Phenotypes: congenital myasthenic syndrome, MONDO:0018940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v5.1 | UNC13A | Tom Hodgkinson reviewed gene: UNC13A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28192369, 39634123.; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.70 | UNC13A | Louise Daugherty edited their review of gene: UNC13A: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.34 | UNC13A | Louise Daugherty reviewed gene: UNC13A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.21 | UNC13A | Louise Daugherty Publications for gene UNC13A were changed from to 27648472 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.15 | UNC13A | Louise Daugherty Mode of inheritance for gene: UNC13A was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.14 | UNC13A | Michael Oldridge reviewed gene: UNC13A: Rating: RED; Mode of pathogenicity: ; Publications: 27648472; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.13 | UNC13A | Louise Daugherty Source NHS GMS was added to UNC13A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.12 | UNC13A |
Louise Daugherty gene: UNC13A was added gene: UNC13A was added to Congenital myaesthenic syndrome. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: UNC13A was set to |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||