Variants in SNAP25 were first reported in relation to developmental and epileptic encephalopathy in 2013 (Rohena et al., 2013, PMID: 25003006). SNAP25 encodes a synaptosomal-associated protein involved in presynaptic and postsynaptic membrane fusion. Clinical features identified in affected individuals include epilepsy, focal clonic and tonic-clonic seizures, variable developmental or intellectual disabilities, hypotonia, ataxia, and minor dysmorphic features.
Thirteen unique variants (missense, nonsense, and splice site) that have been reported in 16 probands in four publications (PMIDs: 25003006, 25381298, 29100083, 33299146) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. Variants are de novo in all probands.
This gene-disease relationship is also supported by experimental evidence, including two mouse models, protein interactions between the v- and t-SNARE complexes, and a rescue model (PMIDs: 2592413, 9529252, 12859899, 17283335).
In summary, there is definitive evidence supporting the relationship between SNAP25 and autosomal dominant developmental and epileptic encephalopathy. This classification was approved by the Intellectual Disability and Autism Gene Curation Expert Panel on March 24, 2022 (SOP Version 8).
Variants in SNAP25 were first reported in relation to developmental and epileptic encephalopathy in 2013 (Rohena et al., 2013, PMID: 25003006). SNAP25 encodes a synaptosomal-associated protein involved in presynaptic and postsynaptic membrane fusion. Clinical features identified in affected individuals include epilepsy, focal clonic and tonic-clonic seizures, variable developmental or intellectual disabilities, hypotonia, ataxia, and minor dysmorphic features.
At least 13 unique missense, nonsense, and splice site variants have been reported in 16 probands included in this curation (PMIDs: 25003006, 25381298, 29100083, 33299146). More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. Variants are de novo in all probands.
This gene-disease relationship is also supported by experimental evidence including two mouse models using blind-drunk mice and SNAP25 affecting the neurons of the mouse hippocampus, protein interactions between the v- and t-SNARE complexes, and lastly, a rescue model (PMID: 2592413, 9529252, 12859899, 17283335).
In summary, SNAP25 is definitively associated with autosomal dominant developmental and epileptic encephalopathy. This classification was approved by the Intellectual Disability and Autism Gene Curation Expert Panel on March 24, 2022 (SOP Version 8).
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